Tachykinin effects on bladder activity in conscious normal rats.
When instilled intravesically in normal, unanesthetized rats, neurokinin A (NKA), but not substance P (SP) and neurokinin B (NKB), stimulated micturition. The effect of NKA was inhibited by the NK2 receptor selective antagonists SR 48,968 and MEN 10,627, but not by the NK1 receptor selective antagonist RP 67,580, suggesting that the effect was mediated by stimulation of NK2 receptors. Given intra-arterially near the bladder, NKA produced an increase in basal intravesical pressure before initiating micturition, indicating that the tachykinin had a direct contractant effect on the detrusor smooth muscle. Such a contractile effect was not observed when NKA was given intravesically. The effect of intra-arterial NKA could not be blocked by the NK1 receptor selective antagonist SR 140,333 or the NK2 receptor selective antagonist SR 48,968, but by their combination. Also intra-arterial NKB stimulated micturition, but was less potent than NKA. Intra-arterial SP had only weak stimulating effects. The results suggest that intravesically administered NKA can initiate micturition in the normal rat by stimulation of superficially located NK2 receptors in the urothelium. Intra-arterially administered NKA caused bladder hyperactivity via stimulation of both NK1 and NK2 receptors.
Ishizuka
O
O
Department of Urology, Lund University Hospital, Sweden.
Mattiasson
A
A
Andersson
K E
KE
D000283:Administration, Intravesical; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D054833:Isoindoles; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D015288:Neurokinin A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015287:Neurokinin B / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects*; D014554:Urination / Q000187:drug effects
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C085215:SR 140333; C090951:MEN 10627; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B