Antagonism of substance P and related peptides by RP 67580 and CP-96,345, at tachykinin NK1 receptor sites, in the rat urinary bladder.

Tonic contraction of rat urinary bladder was elicited in vitro and in vivo by substance P, two selective NK1 receptor agonists, septide ([pGlu6,Pro9]substance P-(6-11)) and [Sar9,Met(O2)11]substance P, and an NK2 agonist, [Lys5,MeLeu9,Nle10]neurokinin A-(4-10), but not by senktide (succinyl[Asp6,MePhe8]substance P-(6-11)), an NK3 agonist. Substance P only stimulated the NK1 receptors of smooth muscle. The non-peptide selective NK1 receptor antagonists, RP 67580 and CP-96,345, both inhibited substance P-induced contraction (pKB values 6.

A non-peptide NK1-receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically.

1. The non-peptide neurokinin NK1-receptor antagonist, RP 67580 (3aR, 7aR), a perhydroisoindolone derivative, powerfully reduced plasma extravasation in rat hind paw skin induced by local application of xylene (ID50 = 0.03 mg kg-1, i.

Effects of the K+ channel activators, RP 52891, cromakalim and diazoxide, on the plasma insulin level, plasma renin activity and blood pressure in rats.

In normo- or hyperglycemic (i.v. infusion of 50 mg/kg/min glucose over 30 min) pithed rats, diazoxide (1 mg/kg/min i.

Increase in plasma renin activity evoked by fenoldopam in dogs is directly mediated by dopamine1 receptor stimulation.

In anesthetized dogs, a 15-min intravenous (i.v.) infusion of fenoldopam (2.