Effects of opioid substances on cAMP response to the β-adrenergic agonist isoproterenol in human mononuclear leukocytes

The effects of different opioid substances on isoproterenol and forskolin-stimulated cyclic AMP (cAMP) intracellular accumulation, and on the binding of 125I-pindodol (IPIN) to β2-adrenoceptors were studied in human mononuclear leukocytes (MNL). The opioids used were α-endorphin, β-endorphin, τ-endorphin, DAGO (a μ receptor agonist), dermenkephalin (a δ receptor agonist and morphine. Only morphine was able to increase the cAMP response to isoproterenol. The EC50 of isoproterenol for cAMP accumulation was shifted leftward by morphine; this effect was blocked by naloxone. On the contrary, the cAMP response to forskolin, direct activator of adenylate cyclase, was similar in the control test with respect to the experiments with morphine. The five opioid peptides induced no changes in the dose-response curves with isoproterenol and forskolin. Furthermore, none of the opioids induced changes in the IPIN binding. Our data show that morphine is able to exert a significant enhancement of the response of β2-adrenergic receptors to isoproterenol in human mononuclear leukocytes. This effect seems to be mediated by μ opioid receptors and seems to involve G protein.