Clinical Focus

  • Nephrology
  • Kidney and Pancreas Transplantation
  • Desensitization and ABO incompatible kidney transplantation

Academic Appointments

Honors & Awards

  • Career Development Award (K23), NIH/NIAID (2012)
  • Nominee, Excellence in Small Group Teaching, UCSF School of Medicine (2007, 2008)
  • Nominee, Kaiser Award for Excellence in Teaching, UCSF School of Medicine (2008)
  • Fellowship, American Society of Nephrology (2008)

Boards, Advisory Committees, Professional Organizations

  • Co-Chair, Education Committee, American Society of Transplantation (2015 - Present)

Professional Education

  • M.T.M., UC Berkeley - UC San Francisco, Translational Medicine (2014)
  • Board Re-certification, American Board of Internal Medicine, Nephrology (2013)
  • Board Re-certification, American Board of Internal Medicine, Internal Medicine (2008)
  • Fellowship:UCLA Medical Center (2005) CA
  • Fellowship:University of Washington (2004) WA
  • Board Certification: Nephrology, American Board of Internal Medicine (2003)
  • Residency:Harbor-UCLA Medical Center (1998) CA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1998)
  • Medical Education:Baylor College of Medicine (1995) TX
  • B.A., UC Berkeley, Physiology, High Honors

Research & Scholarship

Current Research and Scholarly Interests

My research interests are in immune monitoring in kidney transplant patients and in developing new diagnostics. I am interested in translational studies to determine the immunological mechanisms underlying kidney transplant rejection and alloantibody production and to identify novel biomarkers to monitor the immune system in kidney transplant patients. I am also interested in designing novel protocols for desensitization and ABO incompatible kidney transplantation.

Clinical Trials

  • Combined Blood Stem Cell and Kidney Transplant of One Haplotype Match Living Donor Pairs. Recruiting

    The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone marrow Transplantation are enrolling patients into a research study to determine if donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.

    View full details


2014-15 Courses


All Publications

  • ABO-incompatible living donor kidney transplantation without post-transplant therapeutic plasma exchange. Journal of clinical apheresis Yabu, J. M., Fontaine, M. J. 2015


    Blood group incompatibility remains a significant barrier to kidney transplantation. Approximately, one-third of donors are blood group incompatible with their intended recipient. Options for these donor-recipient pairs include blood group incompatible transplantation or kidney paired donation. However, the optimal protocol for blood group incompatible transplantation is unknown. Protocols differ in techniques to remove ABO antibodies, titer targets, and immunosuppression regimens. In addition, the mechanisms of graft accommodation to blood group antigens remain poorly understood. We describe a blood group incompatible protocol using pretransplant therapeutic plasma exchange (TPE), high-dose intravenous immunoglobulin, and rituximab in addition to prednisone, mycophenolate mofetil, and tacrolimus. In this protocol, we do not exclude patients based on a high initial titer and do not implement post-transplant TPE. All 16 patients who underwent this protocol received a living donor transplant with 100% patient and graft survival, and no reported episodes of antibody-mediated rejection to date with a median follow-up of 2.6 years (range 0.75-4.7 years). We conclude that blood group incompatible transplantation can be achieved without post-transplant TPE. J. Clin. Apheresis, 2015. © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jca.21390

    View details for PubMedID 25739580

  • Sensitization from transfusion in patients awaiting primary kidney transplant NEPHROLOGY DIALYSIS TRANSPLANTATION Yabu, J. M., Anderson, M. W., Kim, D., Bradbury, B. D., Lou, C. D., Petersen, J., Rossert, J., Chertow, G. M., Tyan, D. B. 2013; 28 (11): 2908-2918


    Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

    View details for DOI 10.1093/ndt/gft362

    View details for Web of Science ID 000326747600037

    View details for PubMedID 24009295

  • Desensitization Combined With Paired Exchange Leads to Successful Transplantation in Highly Sensitized Kidney Transplant Recipients: Strategy and Report of Five Cases TRANSPLANTATION PROCEEDINGS Yabu, J. M., Pando, M. J., Busque, S., Melcher, M. L. 2013; 45 (1): 82-87


    Sensitization remains a major barrier to kidney transplantation. Sensitized patients comprise 30% of the kidney transplant waiting list but fewer than 15% of highly sensitized patients are transplanted each year. Options for highly sensitized patients with an immunologically incompatible living donor include desensitization or kidney paired donation (KPD). However, these options when used alone may still not be sufficient to allow a compatible transplant for recipients who are broadly sensitized with cumulative calculated panel-reactive antibody (cPRA) > 95%. We describe in this report the combined use of both desensitization and KPD to maximize the likelihood of finding a compatible match with a more immunologically favorable donor through a kidney exchange program. This combined approach was used in five very highly sensitized patients, all with cPRA 100%, who ultimately received compatible living and deceased donor kidney transplants. We conclude that early enrollment in paired kidney donor exchange and tailored desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized patients.

    View details for DOI 10.1016/j.transproceed.2012.08.007

    View details for Web of Science ID 000315007200013

  • Cytomegalovirus in the transplanted kidney: a report of two cases and review of prophylaxis. NDT plus Anand, S., Yabu, J. M., Melcher, M. L., Kambham, N., Laszik, Z., Tan, J. C. 2011; 4 (5): 342-345

    View details for DOI 10.1093/ndtplus/sfr074

    View details for PubMedID 25984184

  • Posttransplantation Anemia: Mechanisms and Management CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yabu, J. M., Winkelmayer, W. C. 2011; 6 (7): 1794-1801


    Treatment of anemia in patients with chronic kidney disease is a topic of increasing interest and controversy. However, anemia in the kidney transplant recipient has received relatively little attention in the literature despite the reported high prevalence of 30% to 40%. The pathogenesis of anemia among kidney transplant recipients is usually multifactorial, including compromised graft function, iron deficiency, immunosuppressive and other medications, and an inflammatory state causing erythropoietin resistance. It is unclear whether posttransplantation anemia is causally linked to cardiovascular events and mortality. Clinicians should screen kidney transplant recipients for posttransplantation anemia and carefully weigh the potential risks and benefits of treatment on an individual basis until well-designed, prospective studies provide further insight. This article reviews the prevalence, pathogenesis, and management of anemia in kidney transplant recipients.

    View details for DOI 10.2215/CJN.01090211

    View details for Web of Science ID 000292618300040

    View details for PubMedID 21734096

  • C1q-Fixing Human Leukocyte Antigen Antibodies Are Specific for Predicting Transplant Glomerulopathy and Late Graft Failure After Kidney Transplantation TRANSPLANTATION Yabu, J. M., Higgins, J. P., Chen, G., Sequeira, F., Busque, S., Tyan, D. B. 2011; 91 (3): 342-347


    Human leukocyte antigen (HLA) antibodies, especially those that fix complement, are associated with antibody-mediated rejection and graft failure. The C1q assay on single antigen beads detects a subset of HLA antibodies that can fix complement and precede C4d deposition. The aim of this study was to determine whether C1q-fixing antibodies distinguish de novo donor-specific antibodies (DSA) that are clinically relevant and harmful.We retrospectively studied 31 of 274 kidney transplant recipients who had pretransplant and concurrent biopsy and serum specimens, 13 with C4d-positive and 18 with C4d-negative staining. We measured IgG and C1q DSA pretransplant and at the time of biopsy using single antigen bead assays. We identified 13 recipients who developed de novo DSA by IgG or C1q and examined associations with C4d deposition, transplant glomerulopathy, and graft failure.Testing for DSA by IgG is more sensitive for C4d deposition (IgG: 100%, 95% confidence interval [CI] 0.60-1; C1q: 75%, 95% CI 0.36-0.96). Testing for DSA by C1q is more specific for transplant glomerulopathy (C1q: 81%, 95% CI 0.57-0.94; IgG: 67%, 95% CI 0.43-0.85) and graft loss (C1q: 79%, 95% CI 0.54-0.93; IgG: 63%, 95% CI 0.39-0.83). Absence of de novo DSA by IgG and C1q has a high negative predictive value for the absence of C4d deposition (IgG: 100%, 95% CI 0.73-1; C1q: 88%, 95% CI 0.62-0.98), transplant glomerulopathy (IgG: 100%, 95% CI 0.73-1; C1q: 100%, 95% CI 0.77-1), and graft failure (IgG: 86%, 95% CI 0.56-0.97; C1q: 88%, 95% CI 0.62-0.98).Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss.

    View details for DOI 10.1097/TP.0b013e318203fd26

    View details for Web of Science ID 000286624400014

    View details for PubMedID 21116220

  • Cytomegalovirus in the transplanted kidney: a report of two cases and review of prophylaxis. Nephrol Dialysis Transplant Plus Anand S, Yabu JM, Melcher ML, Kambham N, Laszik Z, Tan JC 2011; 3 (4): 342-5
  • Lack of alpha 8-integrin aggravates podocyte injury in experimental diabetic nephropathy AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hartner, A., Cordasic, N., Menendez-Castro, C., Volkert, G., Yabu, J. M., Kupraszewicz-Hutzler, M., Rascher, W., Hilgers, K. F. 2010; 299 (5): F1151-F1157


    Development of diabetic nephropathy is accompanied by changes in integrin-mediated cell-matrix interactions. The ?8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, ?8-integrin plays a protective role in the glomerulus. We hypothesized that ?8-integrin is involved in maintaining the integrity of the glomerulus in diabetic nephropathy. Experimental streptozotocin (STZ) diabetes led to an increased expression and glomerular deposition of ?8-integrin. To test the functional role of ?8-integrin, STZ diabetes was induced in mice with a homozygous (?8-/-) or heterozygous (?8+/-) deletion of the ?8-integrin gene and in wild-type litters (?8+/+). Blood glucose and mean arterial blood pressure were not different in ?8-/- and ?8+/+ mice after 6 wk of diabetes. However, diabetic ?8-/- mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic ?8+/+ mice. Moreover, in diabetic ?8-/- mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic ?8+/+. The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in ?8-/- mice. Taken together, ?8-/- mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than ?8+/+ mice, indicating that ?8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy.

    View details for DOI 10.1152/ajprenal.00058.2010

    View details for Web of Science ID 000283846800027

    View details for PubMedID 20826576

  • Kidney Transplantation: The Ideal Immunosuppression Regimen ADVANCES IN CHRONIC KIDNEY DISEASE Yabu, J. M., Vincenti, F. 2009; 16 (4): 226-233


    Kidney transplantation today has excellent short-term outcomes, but long-term graft survival has not improved in a parallel fashion. The goal of immunosuppressive therapy is to balance the beneficial effects of reducing acute rejection while minimizing adverse effects from oversuppression including the development of infections, malignancy, and cardiovascular risk factors. In general, current immunosuppressive protocols use combinations of immunosuppressive agents with different mechanisms of action to maximize efficacy and minimize the toxicity of each drug. During the past decade, there has been a growing interest in identifying regimens that permit the minimization of calcineurin inhibitors or corticosteroids in an attempt to decrease nephrotoxicity and metabolic side effects. The emergence of new immunosuppressive agents and tolerance protocols appear promising as a means to deliver immunosuppression without long-term toxicity. Ultimately, the goal of prescribing immunosuppression is to transition from empiric therapy to one of individualized therapy.

    View details for DOI 10.1053/j.ackd.2009.04.003

    View details for Web of Science ID 000268114400003

    View details for PubMedID 19576552

  • The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation AMERICAN JOURNAL OF TRANSPLANTATION Bluestone, J. A., Liu, W., Yabu, J. M., Laszik, Z. G., Putnam, A., Belingheri, M., Gross, D. M., Townsend, R. M., Vincenti, F. 2008; 8 (10): 2086-2096


    Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL-2 and CD28-CD80/CD86 signaling are critical for CD4(+)CD25(+)FOXP3(+) Treg survival in mice. Yet, both belatacept (a second-generation CTLA-4Ig) and basiliximab (an anti-CD25 monoclonal antibody) are among the arsenal of current immunotherapies being used in kidney transplant patients. In this study, we explored the direct effect of basiliximab and belatacept on the Tregs in peripheral blood both in the short term and long term and in kidney biopsies of patients with acute rejection. We report that the combined belatacept/basiliximab therapy has no long-term effect on circulating Tregs when compared to a calcineurin inhibitor (CNI)-treated group. Moreover, belatacept-treated patients had a significantly greater number of FOXP3(+) T cells in graft biopsies during acute rejection as compared to CNI-treated patients. Finally, it appears that the basiliximab caused a transient loss of both FOXP3(+) and FOXP3(-) CD25(+) T cells in the circulation in both treatment groups raising important questions about the use of this therapy in tolerance promoting therapeutic protocols.

    View details for DOI 10.1111/j.1600-6143.2008.02377.x

    View details for Web of Science ID 000259269900017

    View details for PubMedID 18828769

  • Rituximab failed to improve nephrotic syndrome in renal transplant patients with recurrent focal segmental glomerulosclerosis AMERICAN JOURNAL OF TRANSPLANTATION Yabu, J. M., Ho, B., Scandling, J. D., Vincenti, F. 2008; 8 (1): 222-227


    Focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients with FSGS receiving a first renal transplant and in over 80% of patients receiving a second transplant after a recurrence. Recurrence often leads to graft failure. The pathogenesis remains unknown and may involve a circulating permeability factor that initiates injury to the glomerular capillary. There are anecdotal reports of pediatric patients with posttransplant lymphoproliferative disorder (PTLD) and recurrent FSGS who have had remission of proteinuria after treatment with rituximab. These observations have prompted speculation that B cells may play a role in the pathogenesis of recurrent FSGS. We report four consecutive adult patients with early recurrent FSGS refractory or dependent on plasmapheresis who received rituximab (total dose 2000-4200 mg). None of the patients treated with rituximab achieved remission in proteinuria, and one patient experienced early graft loss. In these four adult renal transplant patients with recurrent FSGS, rituximab failed to diminish proteinuria.

    View details for DOI 10.1111/j.1600-6143.2007.02021.x

    View details for Web of Science ID 000251859400033

    View details for PubMedID 17979998

  • Renal Transplantation Current Diagnosis and Treatment in Nephrology and Hypertension Pham PT, Yabu JM, Pham PC, Wilkinson A 2008: 462-82
  • Novel immunosuppression: Small molecules and biologics SEMINARS IN NEPHROLOGY Yabu, J. M., Vincenti, F. 2007; 27 (4): 479-486


    Kidney transplantation today has excellent short-term outcomes that have paralleled the use of new immunosuppressive agents introduced in the 1990s. In addition to reducing acute rejection, the goals for developing new agents is to improve long-term outcome, minimize nephrotoxicity, and reduce infectious, cardiovascular, and malignancy-related complications. Novel small molecules and biological agents currently in clinical development may help to minimize the use of calcineurin inhibitors and steroids. These small molecules include FTY720, a sphingosine phosphate-receptor modulator, FK778, an inhibitor of pyrimidine synthesis, CP-690550, a JAK3 inhibitor, and AEB-071, a protein kinase C inhibitor. The biological agents include drugs targeting interleukin-15, anti-CD40, belatacept (LEA29Y), a second-generation CTLY4Ig that blocks the interaction between CD80/86 and CD28 costimulatory pathways, and efalizumab, a humanized anti-LFA1 monoclonal antibody. These new agents currently in preclinical and clinical trials appear promising and may represent the emergence of novel immunosuppressive agents that can deliver immunosuppression without long-term toxicity.

    View details for DOI 10.1016/j.semnephrol.2007.03.009

    View details for Web of Science ID 000248206400009

    View details for PubMedID 17616278

  • Genomic organization and sequence variation of the human integrin subunit alpha 8 gene (ITGA8) MATRIX BIOLOGY Ekwa-Ekoka, C., DIAZ, G. A., Carlson, C., Hasegawa, T., Samudrala, R., Lim, K. C., Yabu, J. M., Levy, B., Schnapp, L. M. 2004; 23 (7): 487-496


    The integrin alpha8 is highly expressed during kidney and lung development. alpha8-deficient mice display abnormal renal development suggesting that alpha8 plays a critical role in organogenesis. Therefore, it would be of considerable interest to understand the genomic structure, localization and sequence variation of the alpha8 gene. Using FISH and genomic database analysis, we show that alpha8 gene maps to chromosome 10p13 and consists of >200 kbp organized into 30 exons. Examination of 47 individuals from two different ethnic groups (European and African descent) identified 286 varying sites. The diversity of alpha8 is comparable to that of other regions within the human genome. Eight of the varying sites were located in the coding regions: six resulted in nonsynonymous substitutions of which two lead to non-conservative changes in protein. None of the sites showed significant deviation from Hardy-Weinberg equilibrium. We mapped the coding region single nucleotide polymorphisms (SNPs) onto a model of the predicted alpha8 structure and found all the SNPs were located in the "calf" of the extracellular domain. In the European population, the linkage disequilibrium statistic D' showed three blocks of relatively non-recombinant regions in the alpha8 gene while the African population showed more evidence of recombination. The observed patterns of the linkage disequilibrium statistic R2 suggest that a large number of sites will need to be genotyped to ensure coverage of the entire gene for genetic association studies. Identification of the sequence variation will allow genetic association studies of alpha8 in kidney and lung disease.

    View details for DOI 10.1016/j.matbio.2004.08.005

    View details for Web of Science ID 000226171100008

    View details for PubMedID 15579315

  • Experimental glomerulopathy alters renal cortical cholesterol, SR-B1, ABCA1, and HMG CoA reductase expression AMERICAN JOURNAL OF PATHOLOGY Johnson, A. C., Yabu, J. M., Hanson, S., Shah, V. O., Zager, R. A. 2003; 162 (1): 283-291


    Previous studies indicate that acute tubular injury causes free cholesterol (FC) and cholesteryl ester (CE) accumulation within renal cortex/proximal tubules. This study assessed whether similar changes occur with glomerulopathy/nephrotic syndrome, in which high-circulating/filtered lipoprotein levels increase renal cholesterol supply. Potential adaptive changes in cholesterol synthetic/transport proteins were also assessed. Nephrotoxic serum (NTS) or passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats. Renal injury (blood urea nitrogen, proteinuria) was assessed 2 and 7 days (NTS), or 10 and 30 days (PHN) later. FC and CE levels in renal cortex, isolated glomeruli, and proximal tubule segments were determined. SR-B1 (a CE influx protein), ABCA1 (a FC exporter), and HMG CoA reductase protein/mRNA levels were also assessed. FC was minimally elevated in renal cortex (0 to 15%), the majority apparently localizing to proximal tubules. More dramatic CE elevations were found ( approximately 5 to 15x), correlating with the severity of proteinuria at any single time point (r >/= 0.85). Cholesterol increments were associated with decreased SR-B1, increased ABCA1, and increased HMG CoA reductase (HMGCR) protein and its mRNA. Tubule (HK-2) cell culture data indicated that SR-B1 and ABCA1 levels are responsive to cholesterol supply. Experimental nephropathy can increase renal FC, and particularly CE, levels, most notably in proximal tubules. These changes are associated with adaptations in SR-B1 and ABCA1 expression, which are physiologically appropriate changes for a cholesterol overload state. However, HMGCR protein/mRNA increments can also result. These seem to reflect a maladaptive response, potentially contributing to a cell cholesterol overload state.

    View details for Web of Science ID 000180009800029

    View details for PubMedID 12507911



    Stimulation of cAMP formation in fetal human non-pigmented ciliary epithelial cells by 10 microM prostaglandin E1 was inhibited by 30-50% by 15 min prior exposure to 1 microM phorbol 12-myristate, 13-acetate. Evidence that this inhibition was due to activation of protein kinase C is the following. First, inhibition was also caused by 10 microM dioctanoylglycerol, a diacylglycerol analog. Second, no inhibition was observed using 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, whereas phorbol didecanoate was effective. And third, prior exposure of cells to staurosporine, an inhibitor of protein kinase C, blocked phorbol ester-induced inhibition of cAMP stimulation. Phorbol esters also inhibited stimulation of cAMP formation by 10 nM vasoactive intestinal peptide and by 1 microM isoproterenol. Stimulation of cAMP formation by either 1 microM cholera toxin or 10 microM forskolin was not inhibited by prior exposure of cells to phorbol esters. This suggests that protein kinase C acts neither at the level of GS activation of adenylyl cyclase, nor by inhibiting adenylyl cyclase directly. The possibility that protein kinase C acts on adenylyl cyclase-linked receptors was assessed by measuring the effect of phorbol esters on specific binding of [125I]vasoactive intestinal peptide to intact cells. Treatment of cells with either 1 microM phorbol 12-myristate,13-acetate or phorbol didecanoate resulted in a 25-40% reduction in the number of binding sites for [125I]vasoactive intestinal peptide, with little change in dissociation constants.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994PB36900004

    View details for PubMedID 7835396

  • A Lesson from the Heart American Dragons Yabu JM 1993: 161-6


    Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by approximately 4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20 x 10(-10) and 3 x 10(-10) M, respectively. Prior exposure of cells to 6 x 10(-7) M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanoylglycerol also effectively inhibited, whereas 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a Gs protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C.

    View details for Web of Science ID A1992JV61800027

    View details for PubMedID 1280118



    Several hormones, neurotransmitters, and neuropeptides were screened for the ability to stimulate inositol phosphate formation in cultured human retinal epithelial (RPE) cells. Carbachol, vasopressin and thrombin were found to be effective. Treatment of RPE cells with all three agents produced increases in inositol monophosphate, inositol bisphosphate and inositol trisphosphate in the presence of 10 mM LiCl. Carbachol stimulated a 4-fold increase in the total of inositol phosphates at 1 mM. Studies with cholinergic antagonists showed a rank order of 4 DAMP greater than QNX greater than pirenzepine greater than methoctramine, suggesting the presence of M3 muscarinic receptors. Vasopressin gave a 2.5-fold stimulation at 10 microM. Agonists of vasopressin were also tested and gave differential responses. Studies using a V1 agonist (PIOVP) and a V2 agonist (DAVP) showed DAVP matching the level of stimulation elicited by vasopressin whereas treatment with PIOVP only reached 50% of the vasopressin response. These data suggested the presence of V2 receptors in the RPE cells. Several proteases were tested for their ability to stimulate RPE inositol phosphates. Thrombin caused a 7-fold increase in inositol phosphate formation at 1 U/ml, whereas trypsin and plasmin elicited smaller responses (approximately 2-fold). The thrombin effect was blocked by the thrombin-specific inhibitor, hirudin, but not by other protease inhibitors. Several mediators of inflammation such as bradykinin, histamine and serotonin were also tested, and they were ineffective in stimulating inositol phosphate turnover in the RPE cells.

    View details for Web of Science ID A1992JD61500003

    View details for PubMedID 1380397

Stanford Medicine Resources: