EFFECTS OF OPIOID SUBSTANCES ON CAMP RESPONSE TO THE BETA-ADRENERGIC AGONIST ISOPROTERENOL IN HUMAN MONONUCLEAR LEUKOCYTES

The effects of different opioid substances on isoproterenol and forsko lin-stimulated cyclic AMP (cAMP) intracellular accumulation, and on th e binding of I-123-pindodol (IPIN) to beta 2-adrenoceptors were studie d in human mononuclear leukocytes (MNL), The opioids used were alpha-e ndorphin, beta-endorphin, tau-endorphin, DAGO (a mu receptor agonist), dermenkephalin (a delta receptor agonist and morphine, Only morphine was able to increase the cAMP response ro isoproterenol. The EC(50) of isoproterenol for cAMP accumulation was shifted leftward by morphine; this effect was blocked by naloxone. On the contrary, the cAMP respon se to forskolin, direct activator of adenylate cyclase, was similar in the control rest with respect to the experiments with morphine. The f ive opioid peptides induced no changes in the dose-response curves wit h isoproterenol and forskolin. Furthermore, none of the opioids induce d changes in the IPIN binding. Our data show that morphine is able to exert a significant enhancement of the response of beta 2-adrenergic r eceptors to isoproterenol in human mononuclear leukocytes. This effect seems to be mediated by mu opioid receptors and seems to involve G pr otein.