ELECTRICALLY INDUCED OPIATE-LIKE INHIBITION OF GUINEA-PIG ILEUM - CROSS-TOLERANCE TO MORPHINE

Abstract

The guinea pig myenteric plexus-longitudinal muscle (MPLM) preparation electrically stimulated at 0.1 Hz was very sensitive to the inhibitory effects of opiates. An inhibitory response (IR) was produced by electrical stimulation at 5-20 Hz. The magnitude and duration of IR was determined by the parameters of the stimulation, mainly by the frequency and duration of the period of stimulation. Maximal IR was obtained with symmetrical biphasic stimuli of 2 ms duration and supramaximal voltage at 20 Hz applied for a period of about 5 min. The IR was Ca2+-dependent, could not be attenuated by washing and was mediated by several components, about 55-70% of the IR could be reversed by specific narcotic antagnoists and might be produced by the release of endorphins. There were at least 2 additional components, 1 small, adrenergic in nature and a 2nd one which was not identified. The offset rate of the IR was measured in minutes, while enkephalin and human .beta.-endorphin have half-lives of 10 and 85 s, respectively, after washing. The endorphin that mediates the opiate component of the IR might be a different 1 with slower offset rates. Myenteric plexus-longitudinal muscle strips obtained from guinea pigs which were made tolerant to morphine by s.c. implantation of 3 pellets were cross-tolerant to the opiate component of the IR elicited by electrical stimulation.