Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?
In normal conscious rats investigated by continuous cystometry, intravesically instilled prostaglandin (PG) E2 facilitated micturition and increased basal intravesical pressure. The effect was attenuated by both the NK1 receptor selective antagonist RP 67,580 and the NK2 receptor selective antagonist SR 48,968, given intra-arterially, suggesting that it was mediated by stimulation of both NK1 and NK2 receptors. Intra-arterially given PGE2 produced a distinct increase in bladder pressure before initiating a micturition reflex, indicating that the PG had a direct contractant effect on the detrusor smooth muscle. The effect of intra-arterial PGE2 could not be blocked by intra-arterial RP 67,580 or SR 48,968, which opens the possibility that the micturition reflex elicited by intra-arterial PGE2 was mediated by pathways other than the reflex initiated when the PG was given intravesically. The present results thus suggest that intra-arterial PGE2, given near the bladder, may initiate micturition in the normal rat chiefly by directly contracting the smooth muscle of the detrusor. However, when given intravesically, PGE2 may stimulate micturition by releasing tachykinins from nerves in and/or immediately below the urothelium. These tachykinins, in turn, initiate a micturition reflex by stimulating NK1 and NK2 receptors. Prostanoids may, via release of tachykinins, contribute to both urge and bladder hyperactivity seen in inflammatory conditions of the lower urinary tract.
Ishizuka
O
O
Department of Urology, Lund University Hospital, Sweden.
Mattiasson
A
A
Andersson
K E
KE
D000283:Administration, Intravesical; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003243:Consciousness; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D054833:Isoindoles; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology*
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D018039:Receptors, Tachykinin; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C073839:SR 48968; D015232:Dinoprostone