title: Co-expression 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+.
abstract: The Ca2+-sensing receptor protein and the Ca2+-inhibitable type 6 adenylyl cyclase mRNA are present in a defined segment of the rat renal tubule leading to the hypothesis of their possible functional co-expression in a same cell and thus to a possible inhibition of cAMP content by extracellular Ca2+. By using microdissected segments, we compared the properties of regulation of extracellular Ca2+-mediated activation of Ca2+ receptor to those elicited by prostaglandin E2 and angiotensin II. The three agents inhibited a common pool of hormone-stimulated cAMP content by different mechanisms as follows. (i) Extracellular Ca2+, coupled to phospholipase C activation via a pertussis toxin-insensitive G protein, induced a dose-dependent inhibition of cAMP content (1.25 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 intracellular Ca2+. (ii) Angiotensin II, coupled to the same transduction pathway, also decreased cAMP content; however, its inhibitory effect on cAMP was mainly accounted for by an increase of cAMP hydrolysis, although angiotensin II and extracellular Ca2+ can induce comparable release of intracellular Ca2+. (iii) Prostaglandin E2, coupled to pertussis toxin-sensitive G protein, inhibited the same pool of adenylyl cyclase units as extracellular Ca2+ but by a different mechanism. The functional properties of the adenylyl cyclase were similar to those described for type 6. The results establish that the co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing receptor in a same cell allows an inhibition of cAMP accumulation by physiological concentrations of extracellular Ca2+.
authors.affiliation: Service de Biologie Cellulaire, Département de Biologie Cellulaire et Moléculaire, CEA Saclay, France.
authors.forename: M C
authors.initials: MC
authors.lastname: de Jesus Ferreira
authors.forename: C
authors.initials: C
authors.lastname: Héliès-Toussaint
authors.forename: M
authors.initials: M
authors.lastname: Imbert-Teboul
authors.forename: C
authors.initials: C
authors.lastname: Bailly
authors.forename: J M
authors.initials: JM
authors.lastname: Verbavatz
authors.forename: A C
authors.initials: AC
authors.lastname: Bellanger
authors.forename: D
authors.initials: D
authors.lastname: Chabardès
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000235:genetics*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007672:Kidney Cortex / Q000502:physiology*; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; C473605:extracellular calcium cation-sensing receptor, rat; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D009355:Neomycin; D015232:Dinoprostone; D002118:Calcium