Excitatory and inhibitory cholinergic effects of yohimbine on isolated guinea-pig small intestine.
The interaction of yohimbine with the cholinergic intestinal system was investigated in the isolated guinea-pig ileum using a wide range of drug concentrations from 3 x 10(-13) to 2 x 10(-4) g/ml. Low concentrations of yohimbine (3 x 10(-13) to 3 x 10(-11) g/ml) caused dose-dependent contractions of the ileal longitudinal muscle, which were potentiated by eserine 1 x 10(-8) g/ml and prevented by tetrodotoxin 1 x 10(-6) g/ml or by atropine 1 x 10(-12) g/ml; methysergide and diphenydramine were ineffective up to 3 x 10(-7) g/ml dose. Submaximal stimulatory responses evoked by twitch stimulation or by acetylcholine were significantly potentiated by the same concentrations of yohimbine (3 x 10(-13) to 3 x 10(-11) g/ml) and blocked by atropine 1 x 10(-12) g/ml. By contrast, high concentrations of yohimbine (1 x 10(-6) to 2 x 10(-4) g/ml) displayed dose-dependent inhibitory effects on cholinergic responses. The stimulant effect of yohimbine seems to be indirect and mediated by the increase in the release of acetylcholine, while the inhibitory action may be due to a molecular interaction with the muscarinic receptors allowing non-specific receptor blockade.
Del Tacca
M
M
Institute of Medical Pharmacology, University of Pisa, Italy.
Tadini
P
P
Blandizzi
C
C
Bernardini
M C
MC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology*
D001626:Bethanechol Compounds; D015016:Yohimbine; D000109:Acetylcholine