Cyclic AMP, morphine, met-enkephalin and neuronal firing.
Extracellular recordings were made of spontaneous neuronal firing and of nociceptive stimulus-evoked neuronal firing in the mesencephalic reticular formation of the rat. Microiontophoretically administered morphine and met-enkephalin blocked the nociceptive stimulus-evoked neuronal firing of some neurons in the mesencephalic reticular formation; naloxone antagonized the effects of morphine and met-enkephalin. In neurons in which morphine and met-enkephalin blocked the nociceptive stimulus-evoked firing, the microiontophoretic administration of dibutyryl cyclic AMP (cAMP), 8-bromo cAMP and Ro 20,1724 (a phosphodiesterase inhibitor) consistently (96%) reversed this blockade of evoked firing. The effects of dibutyryl cAMP were specific, because butyrate and 5'-AMP, possible metabolites of the cAMP analog, reversed the blockade by morphine and met-enkephalin of the nociceptive stimulus-evoked neuronal firing much less frequently (29%). These result support the hypothesis that the occupation of opiate receptors triggers an inhibition of the enzyme, adenylate cyclase, as a mechanism of action. The cAMP analogs excited the spontaneous firing in only 60% of the neurons in which they reversed the opioid blockade of pain-evoked firing. This suggests that the mechanism of action of the cAMP analogs on spontaneous firing may differ from that on pain-evoked firing.
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004723:Endorphins; D004745:Enkephalins; D010726:Phosphodiesterase Inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D004744:Enkephalin, Methionine; D009020:Morphine; D000242:Cyclic AMP