Parathyroid hormone-related peptide-(1-34) [PTHrP-(1-34)] induces vasopressin release from the rat supraoptic nucleus in vitro through a novel receptor distinct from a type I or type II PTH/PTHrP receptor.
PTH and PTH-related peptide (PTHrP) bind to a type I PTH/PTHrP receptor expressed in bone and kidney or a type II receptor in nonclassical target tissue with equal affinity and similar bioactivities. PTHrP is abundant in the central nervous system, but its physiological role remains unknown. Herein, we examined the role of PTHrP-(1-34) on arginine vasopressin (AVP) release from the rat supraoptic nucleus (SON). Application of PTHrP-(1-34) to SON slices caused an increase in AVP release in a concentration-dependent manner. Neither PTHrP-(7-34) nor PTH-(1-34) had any effect on AVP release from the SON. PTHrP-(1-34)-induced AVP release was antagonized by a large excess of PTHrP-(7-34) and by H89, an inhibitor of cAMP-dependent protein kinase (A kinase), but not by PTH-(1-34) or PTH-(13-34). PTHrP-(1-34), but not PTH-(1-34), also dose-dependently increased the levels of cAMP in the SON. 125I-Labeled PTHrP-(1-34) bound specifically to crude membranes isolated from the SON. Scatchard analysis showed a single class of binding sites for PTHrP-(1-34) with a Kd of 36.4 nM and a maximum binding capacity of 3.94 pmol/mg protein. No specific binding for 125I-labeled PTH-(1-34) was noted. The binding of 125I-labeled PTHrP-(1-34) was displaced by unlabeled PTHrP-(1-34) and unlabeled PTHrP-(7-34), but not by unlabeled PTH-(1-34). These findings suggest that PTHrP-(1-34), but not PTH-(1-34), causes the release of AVP from the SON through a novel receptor distinct from type I or II PTH/PTHrP receptors.
Yamamoto
S
S
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
Morimoto
I
I
Yanagihara
N
N
Zeki
K
K
Fujihira
T
T
Izumi
F
F
Yamashita
H
H
Eto
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides; D013495:Supraoptic Nucleus / Q000187:drug effects* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D013449:Sulfonamides; C054296:parathyroid hormone-related protein (1-34); D001127:Arginine Vasopressin; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide