Structural requirements for the effects of neuropeptide Y on the hypothalamic-pituitary-adrenal axis in the dog.

Neuropeptide Y (NPY), administered into the third cerebral ventricle of the dog stimulates plasma ACTH and cortisol secretion. To further investigate the structure-activity relationships of this action, we examined the effect of COOH-terminal fragment, NPY 19-36 and its analogues, NPY-(1-36)-OH (deamidated NPY) and avian pancreatic polypeptide (APP) on ACTH-cortisol secretion following intracerebroventricular (i.c.v.) injection in the dog. NPY (1.19 nmol) evoked a significant increase in the secretion of both plasma ACTH and cortisol. However, NPY 19-36 and NPY-(1-36)-OH each failed to increase plasma ACTH and cortisol secretion at doses of 1.19-11.9 nmol injected i.c.v. APP was less active than NPY. These data demonstrate that the entire NPY molecule is required for the full expression of the stimulatory effect of NPY on the secretion of ACTH and cortisol.