STUDIES OF COLON CONTRACTILITY IN DOGS. I. DESCRIPTION OF METHOD AND EFFECT OF PARASYMPATHOMIMETIC AGENTS AND SEROTONIN*†

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Abstract
Using an in vivo intra-arterial injection technique for studying the effect of drugs upon the smooth muscle of the dog colon, the threshold dosage for acetylcholine and methacholine has ranged from 0.001 [mu]g to 0.1 [mu]g and 0.001 [mu]g to 1.0 [mu]g, respectively. Utilizing di-isopropylfluorophos-phate, acute reduction of bowel cholinesterase (43% to 97%) was achieved. This alteration was associated uniformly with augmentation of response to both acetylcholine and methacholine; however, at least 80% inhibition was necessary to alter the threshold dose. The action of 5-hydroxytryptamine (serotonin) and acetylcholine upon the colon of intact, anesthetized dogs was compared. The average threshold dose to induce contraction was the same for each. Atropine was ineffective in blocking serotonin response as compared with acetylcholine, and inhibition of tissue cholinesterase failed to potentiate serotonin effect. Although hexamethonium blocked neither acetylcholine nor serotonin response, mediation of action of these substances via autonomic ganglia is not excluded, since hexamethonium may act at the presynaptic level. Effect of serotonin was enhanced by inhibition of monoamine oxidase and was blocked by both its benzyl analog (BAS) and a phenothiazine derivative, prochlorperazine. Results suggest that when serotonin is administered intra-arterially to an intact colon, it does not act via a cholinergic pathway; however, they do not negate previous evidence that this substance may be a modulator of the cholinergic system.