AVP stimulates adenylyl cyclase and phospholipase C in reciprocal fashion in cultured RIMCT cells

Abstract

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.