AVP stimulates adenylyl cyclase and phospholipase C in reciprocal fashion in cultured RIMCT cells.
In cultured rat inner medullary collecting tubule (RIMCT) cells, arginine vasopressin (AVP) stimulates adenylyl cyclase (AC) activity in dose-dependent fashion, with no response at concentrations of 10(-10) M or below and with peak activity at 10(-7) M AVP. In contrast, AVP-stimulated phospholipase (PLC) activity is greatest at concentrations at which there is no effect on AC and decreases at higher concentrations of AVP, becoming undetectable at 10(-7) M. Increasing cellular adenosine 3',5'-cyclic monophosphate (cAMP) content with either exogenous ClPheScAMP or forskolin eliminates inositol trisphosphate production in response to 10(-13) M AVP. Conversely, inhibition of AC by 2',5'-dideoxyadenosine (DDA) unmasks PLC activity in response to 10(-7) M AVP that is not observed in the absence of DDA. Similarly, DDA prevents inhibition of epidermal growth factor-stimulated PLC by AVP. These findings demonstrate the reciprocal relationship between AVP-stimulated AC and PLC activities in cultured RIMCT cells, which may explain previous divergent results regarding the ability of AVP to stimulate PLC in this tissue.
Teitelbaum
I
I
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Strasheim
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D001127:Arginine Vasopressin; D016048:Dideoxyadenosine; D004815:Epidermal Growth Factor; C021008:2',5'-dideoxyadenosine; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases