Dose-dependent heterogenous actions of vasopressin in rabbit cortical collecting ducts.
In cortical collecting ducts (CCD), arginine vasopressin (AVP) has been proposed to autoinhibit its own hydrosmotic effect through stimulation of prostaglandin (PG) synthesis or binding to a receptor coupled to phosphatidylinositol (PI) hydrolysis, the so-called V1-receptor, with resultant elevation of intracellular Ca2+ concentration [( Ca2+]i) and activation of protein kinase C (PKC). Using isolated perfused rabbit CCD, we examined whether blocking the negative feedback by a PKC inhibitor, staurosporine (SSP), or a cyclooxygenase inhibitor, indomethacin (IND), enhances AVP-induced increase in hydraulic conductivity (Lp). The Lp induced by a pharmacological concentration (23 nM) of AVP was lower than that induced by 230 pM AVP. This blunted Lp response to 23 nM AVP was significantly restored by SSP or IND pretreatment. In contrast, both SSP and IND did not affect the Lp induced by 23 pM or 230 pM AVP. Fluorescence microscopy of isolated perfused CCD using fura-2 showed a spike-like increase in [Ca2+]i only by 23 nM but not by 23 or 230 pM AVP. We conclude that 1) AVP can increase [Ca2+]i, activate PKC, and stimulate PG synthesis in CCD with resultant autoregulation of its own hydrosmotic effect and 2) importantly, however, this negative feedback occurs only with pharmacologically high concentrations of AVP. Therefore it is unlikely that circulating AVP, via binding to receptors on CCD, autoregulates water transport through activating PG synthesis and/or PI breakdown.
Ando
Y
Y
Department of Medicine, Vanderbilt University, Nashville 37232.
Breyer
M D
MD
Jacobson
H R
HR
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006706:Homeostasis; D007213:Indomethacin / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D019311:Staurosporine; D014882:Water-Electrolyte Balance
D000470:Alkaloids; D001127:Arginine Vasopressin; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium; D007213:Indomethacin