Tachykinins and reflexly evoked atropine-resistant motility in the guinea pig colon in vivo.
Distension of a balloon placed in the proximal colon of anesthetized, guanethidine- and naloxone-pretreated guinea pigs elicited a series of long-lasting regular phasic pressure waves which were suppressed by hexamethonium. Activity evoked by a low degree of balloon distension was largely, but not completely, suppressed by atropine. Further balloon distension in atropine-treated animals enabled us to study the effect of tachykinin receptor antagonists on the atropine-resistant and hexamethonium-sensitive response to distension. The selective tachykinin receptor antagonists, (+/-)-CP 96,345 for the NK-1 receptor and L 659,877, MEN 10,376 and SR 48,968 for the NK-2 receptor, inhibited with varying potency the atropine-resistant response to distension. These antagonists also blocked the contraction of the guinea pig colon produced by the i.v. administration of selective NK-1 and NK-2 receptor agonists. In vitro experiments, using mucosa-free circular muscle strips from the guinea pig colon, proved the existence of functional NK-1 and NK-2 receptors in this tissue. We conclude that both NK-1 and NK-2 receptors participate in the atropine-resistant reflex contractions produced by localized balloon distension of the guinea pig colon in vivo.
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
S
S
Giuliani
A
A
Lecci
A
A
Giachetti
C A
CA
Maggi
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin; D015320:Tachykinins / Q000494:pharmacology*
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D001285:Atropine