EFFECT OF DRUGS ON INTESTINAL RELEASE OF STIMULANT ACIDIC LIPIDS IN RELATION TO SIMULTANEOUS DRUG EFFECT ON INTESTINAL MECHANICAL ACTIVITY IN VITRO

¹ Department of Pharmacology, Marquette University School of Medicine, Milwaukee, Wisconsin

The relationship between drug effects in vitro on rabbit intestinal motility, on intestinal motor response to extracts of acidic lipids, and on intestinal release or loss of stimulant lipids has been explored by means of parallel experiments run simultaneously on tissue from the same animals. To determine intestinal release of stimulant lipids, a simple extraction method was employed for the Tyrode solution in which intestine and drug had been incubated, and the extracted stimulant substances were estimated by bioassay.

Dibucaine blocked the motor response of intestine to doses of extract at concentrations which did not significantly alter either spontaneous contractile activity or intestinal release of stimulant lipids. Magnesium ion and cholinergic drugs had marked effects on mechanical activity of intestine without consistently affecting release of stimulant lipids. Epinephrine profoundly inhibited both intestinal release of stimulant lipids and mechanical activity of the tissue. Epinephrine-induced inhibition of motility was antagonized by extracts of acidic lipids, and spontaneous recovery of contractile activity in the presence of high concentrations of epinephrine appeared to depend initially upon substances released from the tissue into the bath. Methoxamine produced less prolonged inhibition of motility and less profound inhibition of stimulant lipid release than did epinephrine. N-Isopropylmethoxamine had only slight effects on contractile activity and no effect on stimulant lipid release, but it blocked both intestinal motor response to extract and the spontaneous recovery of contractile activity in the presence of epinephrine. Reserpine, like epinephrine, inhibited both contractile activity and intestinal release of stimulant lipids. However, reserpine-induced depression of motility was not antagonized by extracts of acidic lipids in the doses employed.

The results of this investigation suggest a functional interrelationship between motor rhythmicity, local tissue adrenergic mechanisms, and local tissue metabolism or lability of certain acidic lipid constituents of intestine in vitro.