Exogenous opiates: their local mechanisms of action in the canine small intestine and stomach

Abstract

Methionine-enkephalin (Met-Enk) and dynorphin were injected intra-arterially into the distal stomach and small intestine of the anesthetized dog during quiescence and phasic activity initiated by field stimulation or intraarterially administered motilin. The effects of morphine, [D-Ala2,N-Me-Phe4,Met(O)5-ol]enkephalin (Met-ol), and [D-Ala2,D-Leu5]enkephalin (DADLE) were also examined. Opiates had no effect on the quiescent stomach but produced inhibition of phasic contractions (potencies: dynorphin > Met-Enk > Met-ol > DADLE > morphine). In the quiescent small intestine, low doses of each opiate, except dynorphin, produced excitation (potencies: Met-Enk .simeq. Met-ol .simeq. DADLE > morphine). Excitation apparently occurred via release of acetylcholine and a partially naloxone-sensitive direct stimulation of smooth muscle. During phasic activity all opiates produced inhibition of phasic muscular contractions (relative potencies as in the stomach). Inhibition by dynorphin in both the stomach and small intestine was shown to occur via naloxone-sensitive inhibition of release of acetylcholine from nerves. Thus inhibition by opiates appears common to the stomach and small intestine, and excitation is a function of opiate action only in the small intestine. Dynorphin may be a natural neuropeptide causing inhibition, and Met-Enk may be a natural neuropeptide causing excitation.