The effect of harmaline and related beta-carbolines on the acetylcholine-stimulated contractions of guinea-pig ileum.
Five members of the Harmala family of alkaloids, four commercially available and one synthetic homologue, were tested for their actions on the acetylcholine-elicited contractions of the guinea-pig ileum. Under normal Tyrode conditions over comparable concentration ranges harmalol was without effect, harmaline and harmine exhibited competitive-noncompetitive inhibition whilst the related 2-methylated derivatives effected purely competitive antagonism. Binding studies using [3H]QNB have further confirmed the competitive aspect of this antagonism. The competitive-noncompetitive inhibitory property of harmaline on smooth muscle muscarinic receptors has not been previously reported. Harmaline is known to compete with Na+ binding sites and significantly complete substitution of Na+ by K+ in the Tyrode medium was found to abolish the noncompetitive component of harmaline inhibition. Explanations are offered for both the competitive and noncompetitive components of the inhibition produced by the Harmala alkaloids.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006246:Harmaline / Q000494:pharmacology*; D007082:Ileum; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007526:Isoelectric Point; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002243:Carbolines; D007211:Indoles; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D006246:Harmaline; D000109:Acetylcholine