Metorphamide, a novel endogenous adrenal opioid peptide, inhibits nicotine-induced secretion from bovine adrenal chromaffin cells.
Opioid peptides are found in high concentrations in the adrenal medulla. Recently, a novel opioid octapeptide, metorphamide, possessing an amidated C-terminal, was characterized and also found to be present in adrenal tissue. We have studied the ability of this novel peptide to modify nicotine-induced secretion from isolated bovine adrenal chromaffin cells. Exocytosis was monitored by measuring adenosine triphosphate (ATP) release on-line by the luciferin-luciferase bioluminescence method, or by measuring endogenous catecholamine release by high-performance liquid chromatography (HPLC) with electrochemical detection. Metorphamide inhibited 5 microM nicotine-induced ATP release from fresh chromaffin cells by almost 50% at 5 microM. Metorphamide at concentrations less than 1 microM had no effect on 5 microM nicotine-induced adrenaline and noradrenaline release from cultured cells, but at higher concentrations inhibited their release equally, with an IC50 of approximately 10 microM. By contrast, Met5-enkephalin inhibited the release of both catecholamines equally with an IC50 of greater than 1 mM, making metorphamide greater than 100-fold more potent than Met5-enkephalin in this system. Naloxone (10 microM) and diprenorphine (1 microM) failed to antagonise the inhibitory action of metorphamide on nicotine-induced catecholamine release. Metorphamide inhibited the nicotinic response in a non-competitive manner, and failed to affect either adrenaline or noradrenaline release induced by elevated potassium ion concentrations. The results suggest metorphamide acts on naloxone- and diprenorphine-resistant receptors to inhibit chromaffin cell nicotinic secretion and that the novel amidated C-terminal of the peptide is important for this action.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D009538:Nicotine / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects
D002395:Catecholamines; D011978:Receptors, Nicotinic; D004744:Enkephalin, Methionine; D009538:Nicotine; C039700:adrenorphin; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D004837:Epinephrine