5-HT1-like receptors mediate potentiation of cholinergic nerve-mediated contraction of isolated mouse trachea.
While it had no effect on the resting tension of mouse tracheal segments, 5-HT (10(-8)-10(-4) M) potentiated concentration dependently the contractions induced by electrical field stimulation (EFS). The maximal potentiation was 105 +/- 38% and the EC50 value was 1.4 +/- 0.6 x 10(-6) M (n = 6). The responsiveness of mouse trachea to acetylcholine was not altered by 5-HT (10(-5) M). The 5-HT1A,B antagonist pindolol (10(-6) M), the combined 5-HT2 and 5-HT1C receptor antagonist, ketanserin (10(-6) M), or the combined 5-HT1 and 5-HT2 receptor antagonist, methysergide (10(-6) M), all partially inhibited the effect of 5-HT on the twitch responses. Blockade of 5-HT3 receptors by GR 38032F (10(-6) M) did not affect the potentiation by 5-HT. Antagonism of 5-HT3 and 5-HT4 receptors by ICS 205,930 (3 x 10(-6) M) increased the potentiation of the twitch responses by 5-HT, this was probably due to a decrease of the baseline EFS-induced twitch response by ICS 205,930. Alkylation of the 5-HT2 receptor by phenoxybenzamine (3 x 10(-7) M) treatment did not significantly affect the potentiation of the twitch responses by 5-HT. The beta-adrenoceptor antagonist, timolol (10(-6) M), and the alpha-adrenoceptor antagonist, phentolamine (10(-6) M), did not influence the potentiation of the twitch responses by 5-HT, excluding the involvement of the adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)
Van Oosterhout
A J
AJ
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
Hofman
G
G
Woutersen-Van Nijnanten
F M
FM
Nijkamp
F P
FP
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D014132:Trachea / Q000294:innervation / Q000502:physiology
D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000109:Acetylcholine