Abstract
A study was designed to examine the intestinal stimulatory effects of 5-hydroxytryptamine (5-HT) in the presence of three types of drugs which are known to decrease intestinal motility. Dog isolated intestinal segments were perfused via the vasculature with Krebs-bicarbonate solution with or without drugs which depress motility: adrenergic amines, prostaglandin E1 and theophylline. The excitatory agonists tested were 5-HT, bethanechol and dimethylphenylpiperazinium (DMPP). Isoproterenol (1 and 5 µg/ml) shifted the 5-HT dose-response curve to the right but did not affect intestinal contractions produced by the cholinergic agonists, bethanechol and DMPP. Prostaglandin E1 (1 µg/ml) did not alter responses to bethanechol, but caused a slight decrease in responses to DMPP. The prostaglandin shifted the 5-HT dose-response curve to the right. Theophylline (180 µg/ml) had no effect on responses to bethanechol or DMPP but produced a shift to the right in the dose-response curve for 5-HT. Norepinephrine (0.1 and 0.2 µg/ml) had no effect on responses to bethanechol, but produced shifts to the right in dose-response curves for DMPP and 5-HT. Methoxamine (10 and 50 µg/ml) caused effects similar to those produced by norepinephrine. These data indicate that beta adrenergic agonists, prostaglandin E1 and theophylline, which have in common the ability to increase intestinal cyclic adenosine monophosphate (cyclic AMP), antagonize motility responses to 5-HT but have little or no effect on motility responses to cholinergic agonists. The effect of norepinephrine on DMPP can be explained in terms of alpha adrenergic receptor actions since methoxamine had similar effects on DMPP responses. It is hypothesized that 5-HT produces contractions of intestinal smooth muscle by somehow lowering intracellular levels of cyclic AMP or by blocking cyclic AMP inhibitory effects.
Footnotes
- Received August 14, 1973.
- Accepted January 18, 1974.
- © 1974 by The Williams & Wilkins Co.
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