title: Neuronal and adrenal enkephalins and catecholamines in response to acute CNS ischemia and reserpine in pig.
abstract: Co-storage of enkephalins and catecholamines in coronary artery, mesenteric artery and vein, middle cerebral artery, vas deferens and adrenal medulla was studied in domestic pig (Sus scrofa). Responses to acute CNS ischemia were correlated with time to peak plasma levels of central venous and adrenal vein outflow samples in controls, during reserpine treatment and after drug withdrawal. Endogenous enkephalins are co-stored in chromaffin granules of adrenal epinephrine-type cells and large dense cored vesicles of noradrenergic terminals. After a lag period, reserpine at near 'therapeutic' doses caused an apparent induction of opioid peptide precursor synthesis accompanied by processing to enkephalins in adrenal medulla up to 8-fold by 30 days and in mesenteric vein up to 4.5-fold by 14 days. Upon 14 days recovery from reserpine, elevated adrenal enkephalins were maintained and depleted catecholamines were largely replenished. Acute CNS ischemia produced rises in MAP (approx. 80 mmHg), marked net depletions of noradrenergic enkephalin stores, and net increases in adrenal vein outflow and central venous levels of enkephalins and catecholamines. Noradrenergic terminals contributed significantly to circulating enkephalins as well as norepinephrine. Reserpine for 7 days nearly abolished all tested responses to acute CNS ischemia, but immediate net 200-400% elevations of endogenous enkephalin stores occurred in coronary artery and mesenteric artery and vein (apparent processing of reserpine-induced neuronal precursor stores). Thus, induction of new synthesis of precursor opioid peptides by reserpine, with or without parallel processing to enkephalins, occurs in noradrenergic terminals in many tissues. All effects of reserpine on endogenous enkephalins implicate a central mechanism to inhibit sympathoadrenal outflow to the periphery. At 14 days recovery from reserpine, when near normal cardiovascular responses to acute CNS ischemia were regained, there was increased net release of the elevated adrenal enkephalins, exaggerated peak plasma enkephalin concentrations, but only minimal depletions of enkephalins from noradrenergic terminals.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
authors.forename: R L
authors.initials: RL
authors.lastname: Klein
authors.forename: R W
authors.initials: RW
authors.lastname: Duncan
authors.forename: T J
authors.initials: TJ
authors.lastname: Selva
authors.forename: J Y
authors.initials: JY
authors.lastname: Kong
authors.forename: A
authors.initials: A
authors.lastname: Thureson-Klein
mesh_terms: D000208:Acute Disease; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D002490:Central Nervous System / Q000098:blood supply*; D004745:Enkephalins / Q000097:blood / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013552:Swine; D014018:Tissue Distribution
chemical_list: D002395:Catecholamines; D004745:Enkephalins; D012110:Reserpine