Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jun;148(6):2854-62.
doi: 10.1210/en.2007-0189. Epub 2007 Mar 15.

Direct Evidence That Stimulation of Neuropeptide Y Y5 Receptor Activates Hypothalamo-Pituitary-Adrenal Axis in Conscious Rats via Both Corticotropin-Releasing Factor- And Arginine Vasopressin-Dependent Pathway

Affiliations

Direct Evidence That Stimulation of Neuropeptide Y Y5 Receptor Activates Hypothalamo-Pituitary-Adrenal Axis in Conscious Rats via Both Corticotropin-Releasing Factor- And Arginine Vasopressin-Dependent Pathway

Nobukazu Kakui et al. Endocrinology. .

Abstract

An abundance of data suggests a crucial role of neuropeptide Y (NPY) as an activator of the hypothamamo-pituitary-adrenal (HPA) axis. However, there is quite limited evidence regarding receptors that mediate this response. Here, we address the possibility that Y(5) receptor subtype may be responsible for NPY-induced activation of HPA axis. For this purpose, the effects of an intracerebroventricular injection of Y(5)-selective agonist, [cPP(1-7), NPY(19-23), Ala(31), Aib(32), Gln(34)]-human pancreatic polypeptide (hPP), on circulating ACTH and corticosterone in conscious rats were evaluated. Central injection of hPP (100 pmol) produced significant increases in plasma ACTH and corticosterone compared with artificial cerebrospinal fluid, and previous treatment with a novel Y(5)-selective antagonist, FMS586 [3-(9-isopropyl-6,7,8,9-tetrahydro-5H-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride] (25 mg/kg, po), completely blocked these alterations. Pretreatment with corticotropin-releasing factor (CRF) receptor antagonist (astressin, 10-50 microg/rat, iv) or arginine vasopressin (AVP) receptor antagonist ([deamino-Pen(1), O-Me-Tyr(2), Arg(8)] vasopressin; 3-30 microg/rat, iv) differentially suppressed these increases by 70-80 or 40-50%, respectively. The combined treatment showed no additive effect of these antagonists. Furthermore, an exogenous AVP (0.3 microg/rat, iv)-induced HPA activation was fully inhibited by astressin, suggesting a convergent pathway of AVP receptor signals onto CRF neurons. Central injection of hPP also evoked marked up-regulation of mRNA expression for CRF and AVP in the hypothalamus, which, likewise, were completely reversed by FMS586. Our observations provide the first evidence that selective stimulation of Y(5) receptor provokes activation of the HPA axis and its downstream pathway is chiefly composed of both CRF (primary regulator) and AVP (subordinate to the former) with distinct relative contribution.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

MeSH terms

Substances

Feedback