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 recepto r expressed in bone and kidney or a type II receptor in nonclassical t arget tissue with equal affinity and similar bioactivities. PTHrP is a bundant in the central nervous system, but its physiological role rema ins unknown. Herein, we examined the role of PTHrP-(1-34) on arginine vasopressin (AVP) release from the rat supraoptic nucleus (SON). Appli cation 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-(l-SC)-induced A VP release was antagonized by a large excess of PTHrP-(7-34) and by H8 9, an inhibitor of cAPMP-dependent protein kinase (A kinase), but not by PTH-(1-34) or PTH-(13-34). PTHrP-(1-34), but not PTH-(1-34), also d ose-dependently increased the levels of cAMP in the SON. I-125-Labeled PTHrP-(1-34) bound specifically to crude membranes isolated fr om the SON. Scatchard analysis showed a single class of binding sites for PT HrP-(1-34) with a K-d of 36.4 nM and a maximum binding capacity of 3.9 4 pmol/mg protein. No specific binding for I-125-Iabeled PTH-(1-34) wa s noted. The binding of I-125-labeled PTHrP-(1-34) was displaced by un labeled PTHrP-(1-34) and unlabeled PTHrP-(7-34), but not by unlabeled PTH-(1-34). These findings suggest that PTHrP-(1-34), but not PTK(1-34 ), causes the release of AVP from the SON through a navel receptor dis tinct from type I or II PTH/PTHrP receptors.