Interactions of methylxanthines, nonxanthine phosphodiesterase inhibitors, and calcium with morphine in the guinea pig myenteric plexus

Publisher Website
Google Scholar
Abstract
In an earlier study, theophylline was shown to antagonize the morphine-induced inhibition of electrically induced contractions of the longitudinal muscle – myenteric plexus preparation from the guinea pig ileum. In the present study, acetylcholine (ACh) released from the myenteric plexus was measured directly using a radioenzymatic assay. Theophylline antagonized the morphine-induced inhibition of ACh release. A similar antagonism was also observed with caffeine and 3-isobutyl-1-methylxanthine (IBMX). All three methylxanthines also increased ACh release. The nonxanthine phosphodiesterase (PDE) inhibitors 4-(3-butoxy-4-methoxy)-2-imidazolidinone (Ro 20-1724) and 1-ethyl-4-isopropylidenehydrazino-1H-pyrozolo(3,4-b)-pyridine-5-carboxylate, ethylester, HCl (SQ 20,009) generally did not antagonize the morphine-induced inhibition of ACh release. The PDE inhibitor SQ 20,009, but not Ro 20-1724, enhanced the release of ACh. Both high calcium concentration and the divalent cation ionophore A23187 antagonized the inhibitory action of morphine on ACh release. These observations suggest that alteration in calcium fluxes rather than the inhibition of PDE mediate the methylxanthine-induced antagonism of morphine in this preparation.

This publication has 2 references indexed in Scilit: