Centrally administered parathyroid hormone (PTH)-related protein(1-34) but not PTH(1-34) stimulates arginine-vasopressin secretion and its messenger ribonucleic acid expression in supraoptic nucleus of the conscious rats.
It has been suggested that PTH-related protein (PTHrP) is an endogenous modulator of cardiovascular systems. We have reported that PTHrP(1-34), but not PTH(1-34), causes the release of arginine-vasopressin (AVP) from the supraoptic nucleus (SON) of the hypothalamus in vitro through a novel receptor distinct from the PTH/PTHrP receptors (type I or type II) described previously. In this study, we have investigated the in vivo effects of PTHrP(1-34) on AVP secretion and its, messenger RNA (mRNA) expression in the SON in conscious rats. Intracerebroventricular (i.c.v.) administration of PTHrP(1-34) resulted in an increase in plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after i.c.v. administration of PTHrP(1-34). Neither PTHrP(7-34) nor PTH(1-34) had any effect on plasma AVP levels. PTHrP(1-34)-induced AVP secretion was antagonized by pretreatment with PTHrP(7-34) but not by that with PTH(1-34). In addition, in situ hybridization study revealed that AVP mRNA expression in the SON and paraventricular nucleus was significantly increased 30 min after i.c.v. administration of PTHrP(1-34) and reached a maximum at 180 min. Furthermore, in Northern blot analyses, AVP mRNA expression in the SON was increased to approximately a 2-fold of basal level by PTHrP(1-34). On the other hand, neither PTHrP(7-34) or PTH(1-34) had any effect on the mRNA expression. The PTHrP(1-34)-stimulated AVP mRNA expression was eliminated by pretreatment with PTHrP(7-34) but not with PTH(1-34). These results suggest that, in the central nervous system, PTHrP(1-34) is involved in AVP secretion through a novel receptor distinct from the PTH/PTHrP receptors reported previously, playing a role in the body water and electrolyte homeostasis.
Yamamoto
S
S
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Morimoto
I
I
Zeki
K
K
Ueta
Y
Y
Yamashita
H
H
Kannan
H
H
Eto
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000502:physiology; D013495:Supraoptic Nucleus / Q000378:metabolism*; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*
D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide; D001127:Arginine Vasopressin