Substance P(6-11) and natural tachykinins interact with septide-sensitive tachykinin receptors coupled to a phospholipase C in the rat urinary bladder.
The rat urinary bladder possesses NK1, NK2 (but not NK3) and 'septide-sensitive' tachykinin receptors coupled to a phospholipase C. The present study performed with SR48968 (10(-6) M) to avoid any interaction of the tested peptides with NK2 receptors, indicates that substance P(6-11) (with a high potency), neurokinin A, neurokinin B and to a lesser extent neuropeptide K (with a lower potency) stimulate [3H]-inositol monophosphate ([3H]-IP1) formation in this tissue by acting on the 'septide-sensitive' tachykinin receptors. Substance P(6-11) had little affinity for NK1 binding sites and stimulated [3H]-IP1 formation with an EC50 value and a maximal amplitude similar to those of septide. As previously observed with septide, this maximal response of substance P(6-11) (insensitive to 10(-6) M SR48968) which was about three-fold that of substance P, was blocked by the NK1 receptor antagonist RP67580 and prevented by [Pro9]substance P (NK1 receptor agonist). Similarly, substance P and several substance P C-terminal fragments prevented the substance P(6-11)-evoked response. In addition, neurokinin A, neuropeptide K and neurokinin B induced SR48968-resistant responses which exhibited a maximal amplitude similar to that of substance P (6-11) and were blocked by RP67580 and totally or partially (neuropeptide K) prevented by [Pro9]substance P.
Torrens
Y
Y
Collège de France, INSERM U 114, Paris, France.
Saffroy
M
M
Glowinski
J
J
Beaujouan
J C
JC
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D015288:Neurokinin A / Q000378:metabolism / Q000494:pharmacology; D015287:Neurokinin B / Q000378:metabolism / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D015320:Tachykinins; D014316:Tritium; D010738:Type C Phospholipases / Q000378:metabolism*; D001743:Urinary Bladder / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*
D000700:Analgesics; D001549:Benzamides; D007295:Inositol Phosphates; D009479:Neuropeptides; D010446:Peptide Fragments; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; D015320:Tachykinins; C045206:neuropeptide K; D014316:Tritium; C067285:substance P, Pro(9)-; D013373:Substance P; C032292:substance P (6-11); C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; D010738:Type C Phospholipases; D011761:Pyrrolidonecarboxylic Acid