Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats.
We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.
Noguchi
M
M
Kampo and Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. noguchi_masamichi@mail.tsumura.co.jp
Ikarashi
Y
Y
Yuzurihara
M
M
Mizoguchi
K
K
Kurauchi
K
K
Chen
J-T
JT
Ishige
A
A
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D019584:Hot Flashes / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology; D023421:Models, Animal; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D012881:Skin Temperature / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide