The effect of 4-aminopyridine on micturition reflex in normal or capsaicin-desensitized rats.
4-aminopyridine (4-AP) produced a dose-related (0.15-2 mg/kg i.v.) potentiation of the voiding cycle of the urinary bladder and increased frequency of micturition in urethane-anesthetized rats. In bladders containing a subthreshold amount of fluid for eliciting reflex micturition 4-AP (1-3 mg/kg i.v.) activated a series of high-amplitude, hexamethonium-sensitive rhythmic bladder contractions. In rats desensitized to capsaicin as newborns, reflex micturition was almost abolished: in these animals i.v. 4-AP did not affect bladder voiding unless at high doses (1-2 mg/kg), at which a reversal from anesthesia occurred. This was accompanied by a prompt micturition. In unanesthetized rats, neither the 4-AP-induced convulsions nor the behavioral response (assessed in an open field) to 4-AP were affected by neonatal capsaicin desensitization. Daily urine production of capsaicin-pretreated animals did not differ from that of controls. However, when measurements were made during daytime, almost no spontaneous urine emission was found in capsaicin-treated rats. On the rat isolated urinary bladder, 4-AP potentiated the response to field stimulation in preparations from both vehicle- and capsaicin-pretreated animals. These findings indicate that 4-AP has a potent excitatory action on bladder voiding in rats and support the hypothesis that in this species 'conscious' bladder voiding can be initiated through capsaicin-resistant mechanisms.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Santicioli
P
P
Borsini
F
F
Giuliani
S
S
Conte
B
B
Lecci
A
A
Meli
A
A
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012018:Reflex / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014554:Urination / Q000187:drug effects*
D000631:Aminopyridines; D015761:4-Aminopyridine; D002211:Capsaicin