Peptide analogue studies of the hypothalamic neuropeptide Y receptor mediating pituitary adrenocorticotrophic hormone release

被引：54

作者：

Small, CJ ^{[1
]}

Morgan, DGA ^{[1
]}

Meeran, K ^{[1
]}

Heath, MM ^{[1
]}

Gunn, I ^{[1
]}

Edwards, CMB ^{[1
]}

Gardiner, J ^{[1
]}

Taylor, GM ^{[1
]}

Hurley, JD ^{[1
]}

Rossi, M ^{[1
]}

Goldstone, AP ^{[1
]}

OShea, D ^{[1
]}

Smith, DM ^{[1
]}

Ghatel, MA ^{[1
]}

Bloom, SR ^{[1
]}

机构：

[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED,DIV ENDOCRINOL & METAB MED,LONDON W12 0NN,ENGLAND

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1997年 / 94卷 / 21期

基金：

英国惠康基金;

关键词：

intracerebroventricular; hypothalamus; hypothalamo-pituitary-adrenal axis;

D O I：

10.1073/pnas.94.21.11686

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hypothalamic neuropeptide Y (NPY) is thought to be important in the regulation of feeding and also in the release of Adrenocorticotrophic hormone (ACTH). Intracerebroventricular administration of NPY to male rats significantly increased plasma ACTH 10 min after injection and stimulated 2-h food intake. A series of analogues of NPY that have a greatly reduced affinity for the Y1 [human pancreatic polypeptide (human PP), NPY(3-36)], the Y2 ([Pro(34)]NPY human PP), the Y3 (peptide YY), and the Y6 (human PP) receptor, all markedly stimulated ACTH release. Rat PP, which binds with high affinity to the Y4 receptor, was unable to stimulate ACTH release. A novel analogue fragment [pro(34)]NPY(13-36) was synthesized as a ligand with low Y1 and Y2 receptor affinity. Interestingly, neither [Pro(34)]NPY(13-36) nor the selective Y5 receptor agonist [D-Trp(32)]NPY stimulated food intake, whereas both significantly increased plasma ACTH. Thus the hypothalamic NPY receptor mediating increases in plasma ACTH has a fragment activation profile unlike the Y1-Y4 or Y6 receptors and appears distinct from the NPY receptor controlling food intake.

引用

页码：11686 / 11691

页数：6

共 49 条

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