INVOLVEMENT OF SEPTIDE-SENSITIVE TACHYKININ RECEPTORS IN INOSITOL PHOSPHOLIPID HYDROLYSIS IN THE RAT URINARY-BLADDER

The selective NK? agonist [Lys(5),MeLeu(9),Nle(10)]NKA(4-10) markedly stimulated [H-3]inositol monophosphate (IPI) formation in prisms from the rat urinary bladder. This response was blocked by the NK, antagonist SR 48968. Senktide (NK, agonist) was inactive. Septide, a short SP analogue, and the NK1 agonists [Pro(9)]SP and [Sar(9)]Met(O-2)(11)]SP also stimulated [H-3]IP1 formation and several NKI tachykinin antagonists (RP 67580, CP 96345, GR 82334, and [D-Pro(9), t beta-BPr10,Trp(11)]SP) were more potent in blocking the septide than the [Pro(9)]SP response. GR 82334 was the most discriminative. SR 48968 (10(-6) M) shifted the [Pro(9)]SP dose-response curve but did not modify the septide dose-response curve. Septide had a low affinity for [H-3][Pro(9)]SP binding sites, suggesting further that septide and NKI agonists act on different receptors. Finally, both [Pro(9)]SP and [Sar(9),Met(O-2)(11)]SP blocked the septide-evoked response, acting as partial agonists at the septide-sensitive tachykinin receptors.