Cyclic adenosine monophosphate and diacylglycerol. Mutually inhibitory second messengers in cultured rat inner medullary collecting duct cells.

Abstract

Studies were performed to examine interactions between the adenylyl cyclase (AC) and phospholipase C (PLC) signaling systems in cultured rat inner medullary collecting duct cells. Stimulation of AC by either arginine vasopressin (AVP) or forskolin or addition of exogenous cAMP inhibits epidermal growth factor (EGF)-stimulated PLC. This inhibition is mediated by activation of cAMP-dependent kinase as it is prevented by pretreatment with the A-kinase inhibitor, N-12-(methylamino)ethyll-5-isoquinoline-sulfonamide (H8) but not by the C-kinase inhibitor, 145-isoquinolinylsulfonyl)-2-methylpiperazine (H7). Exposure to EGF eliminates AVPstimulated cAMP generation. This is not mediated by a cyclooxygenase product as inhibition by EGF is observed even in the presence of the cyclooxygenase inhibitor, flurbiprofen. Inhibition by EGF is not due to an increase in inositol trisphosphate (IP3) as exposure of saponin-permeabilized cells to exogenous IP3 is without effect. Inhibition by EGF is prevented by pretreatment with the C-kinase inhibitor, H7, but not by the A-kinase inhibitor, H8. Exposure to the synthetic diacylglycerol (DAG), dioctanoylglycerol, also inhibits AVP-stimulated AC activity; therefore, inhibition by EGF is due to activation of protein kinase C. Thus, in cultured rat inner medullary collecting duct cells, cAMP and DAG function as mutually inhibitory second messengers with each impairing formation of the other.

Vasopressin resistance in chronic renal failure. Evidence for the role of decreased V2 receptor mRNA.

“…It should be noted, however, that in that study both the severity and duration of uremia were substantially less than in the study by Fine et The rat IMCD has been reported to express VIa receptor mRNA the level of which, in contrast to that of V2 receptor mRNA, is not decreased when plasma AVP increases during dehydration (36). VIa receptor occupancy might promote phosphoinositide hydrolysis with subsequent stimulation of PKC which has been shown by us and others to impair the hydroosmotic response to AVP (32,37,38 This study did not address the mechanism(s) responsible for the decreases in V2 receptor mRNA and apparent number. The available data does not allow us to exclude the possibility of decreased stability of V2 receptor mRNA.…”

Hyponatremia in cirrhosis: From pathogenesis to treatment†

“…Cellular pathways known to be involved in the inhibition of VP signaling are protein kinase C and the extracellularly regulated protein kinases. [41][42][43][44] VP AND VP RECEPTORS VP Biosynthesis: the VP Gene. VP is synthesized in neurons of the supraoptic and paraventricular nuclei.…”

Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C.

“…EGF fails to stimulate PLC in either renal cortical slices (6) or glomerular mesangial cells (7). Yet it has been shown that EGF, via activation of protein kinase C, modulates the response to vasopressin in both rabbit cortical collecting tubule (8) and cultured rat inner medullary collecting tubule (RIMCT) cells (9). The present study was therefore undertaken to determine whether EGF is capable of stimulating PLC activity in cultured RIMCT cells and to examine the roles of guanine nucleotides, extra-and intracellular calcium, and protein kinase C in regulating EGF-stimulated phosphoinositide hydrolysis in this tissue.…”