COEXPRESSION OF A CA2-INHIBITABLE ADENYLYL-CYCLASE AND OF A CA2+-SENSING RECEPTOR IN THE CORTICAL THICK ASCENDING LIMB CELL OF THE RAT-KIDNEY - INHIBITION OF HORMONE-DEPENDENT CAMP ACCUMULATION BY EXTRACELLULAR CA2+()

The Ca2+-sensing receptor protein and the Ca2+-inhibitable type 6 aden ylyl cyclase mRNA are present in a defined segment of the sat renal tu bule leading to the hypothesis of their possible functional co-express ion in a same cell and thus to a possible inhibition of cAMP content b y extracellular Ca2+. By using microdissected segments, we compared th e properties of regulation of extracellular Ca2+-mediated activation o f Ca2+ receptor to those elicited by prostaglandin E-2 and angiotensin II. The three agents inhibited a common pool of hormone-stimulated cA MP content by different mechanisms as follows. (i) Extracellular Ca2+, coupled to phospholipase C activation via a pertussis toxin-insensiti ve G protein, induced a dose-dependent inhibition of cAMP content (1.2 5 mM Ca2+ eliciting 50% inhibition) resulting from both stimulation of cAMP hydrolysis and inhibition of cAMP synthesis; this latter effect was mediated by capacitive Ca2+ influx as well as release of intracell ular Ca2+. (ii) Angiotensin II, coupled to the same transduction pathw ay, also decreased cAMP content; however, its inhibitory effect on cAM P was mainly accounted for by an increase of cAMP hydrolysis, although angiotensin II and extracellular Ca2+ can induce comparable release o f intracellular Ca2+. (iii) Prostaglandin E-2, coupled to pertussis to xin-sensitive G protein, inhibited the same pool of adenylyl cyclase u nits as extracellular Ca2+ but by a different mechanism, The functiona l properties of the adenylyl cyclase were similar to those described f or type 6. The results establish that the co-expression of a Ca2+-inhi bitable adenylyl cyclase and of a Ca2+-sensing receptor in a same cell allows an inhibition of cAMP accumulation by physiological concentrat ions of extracellular Ca2+.