|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1993 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1992 : ¥1,500,000 (Direct Cost : ¥1,500,000)
1. Central cardiovascular regulalion of tachykinin peptides :
In anesthetized rats, the central administration of substance P, neurokinin A and neuropeptide gammma which derived from the preprotachykinin A gene, increased the blood pressure and heart rate by effects mediated by the sympathetic nerve activity, whereas central administration of neurokinin B, derived from the preprotachykinin B gene, increased the blood pressure via secretion of vasopressin from pituitary. In addition, a non-peptide antagonist of NK-1 receptor, CP-96,345 (200 nmol, i.c.v.) inhibited the pressor responses to the NK-1 receptor-selective agonist GR 73632 (0.5 nmol, i.c.v.) and substance P (7 nmol, i.c.v.). It also inhibited the increase in blood pressure elicited by neurokinin A (7 nmol, i.c.v.). However, it had no effect on the earlier pressor response induced by neuropeptide gammma (1 nmol, i.c.v.) or by a selective NK-3 agonist senktide (1 nmol, i.c.v.). These findings suggest that substance P (i.c.v.) induces pressor responsed via NK-1 receptor, and that the pressor response to neurokinin A may also be mediated by the NK-1 receptor in the brain.
2. The antidiuretic action of central tachykinin peptides :
Intracerebroventricular (i.c.v.) injections of senktide (0.01-10 nmol), a tachykinin NK-3 agonist, had an antidiuretic action in water-loaded rats (4.5% body wt.). Pretreatment with OPC-31260 (1 mg/kg, i.v.), a non-peptide vasopressin V2 antagonist, inhibited the antidiuretic action induced by exogenous arginine vasopressin (AVP, 0.1 ug/kg, i.v.) and senktide (0.1 nmol, i.c.v.). In addition, senktide (11.8 nmol, i.c.v.) caused a marked increase of the plasma AVP level in conscious rats. These results suggest that the central neurokinin B analogue senktide has an antidiuretic effect by stimulating AVP secretion from the pituitary gland through the NK-3 receptor in the hypothalamus.