Evidence that atypical vasopressin V(2) receptor in inner medulla of kidney is V(1B) receptor.
Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for the V(2)-like receptor, which evokes an increase in [Ca(2+)](i) when stimulated by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) in kidney inner medullary collecting duct. We compared the pharmacological characteristics of vasopressin V(2) and V(1B) receptors in Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in rat inner medullary collecting duct cells. The vasopressin V(1B) receptor-selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin (D3PVP) did not stimulate the [Ca(2+)](i) increase in high-density vasopressin V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2-phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors, did not block the [Ca(2+)](i) increase in inner medullary collecting duct cells when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was detected only in the medulla. We propose that the true nature of the vasopressin V(2)-like receptor in the inner medullary collecting duct is the vasopressin V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high-density.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Ibaraki 305-8585, Tsukuba, Japan. saito@yamanouchi.co.jp
M
M
Saito
A
A
Tahara
T
T
Sugimoto
K
K
Abe
K
K
Furuichi
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012076:Renal Agents / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D001552:Benzazepines; D007211:Indoles; D007295:Inositol Phosphates; D009025:Morpholines; D011759:Pyrrolidines; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D012076:Renal Agents; D013141:Spiro Compounds; C106389:conivaptan; D014667:Vasopressins; C103281:satavaptan; C082134:relcovaptan; D003894:Deamino Arginine Vasopressin; D002118:Calcium