title: Opioid receptor stimulation suppresses the adrenal medulla hypoxic response in sheep by actions on Ca(2+) and K(+) channels.
abstract: Before the preganglionic regulation of the adrenal medulla is established, hypoxia acts directly on the chromaffin cells to evoke the secretion of catecholamines. This direct action of hypoxia is suppressed by the gradual development of the preganglionic innervation and we have proposed that opioid peptides released from the adrenal splanchnic nerves may be responsible for this suppression. The effects of the specific opioid agonists DPDPE (delta-agonist), U-62066 (kappa-agonist) and DALDA (mu-agonist) on the hypoxia-evoked response were investigated in both a whole-gland preparation and in isolated adrenal chromaffin cells using amperometry, whole-cell patch clamping and measurement of cytosolic [Ca(2+)]. The combined application of mu- and kappa-type agonists abolished the hypoxia-evoked catecholamine secretion from whole perfused adrenal gland. In isolated chromaffin cells, mu- and kappa-opioid agonists reduced the rise in [Ca(2+)](i) that results from exposure to hypoxia. Both agonists decreased the voltage-dependent Ca(2+) current in these cells. The mu-agonist increased the conductance through SK-type K(+) channels and this action offset the decrease in K(+) conductance produced by exposure to hypoxia. The kappa-type agonist decreased the conductance through an action on BK-type K(+) channels, a class of channels that are not involved in initiating the direct response to hypoxia. These data suggest that opioids, through their action on SK channels and voltage-dependent Ca(2+) channels, may be responsible for the nerve-induced suppression of the hypoxic response of adrenal chromaffin cells and that these effects of endogenous opioids are mediated via mu- and kappa-type receptors.
authors.affiliation: Discipline of Physiology, University of Adelaide, Adelaide 5005, Australia.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.forename: Grigori Y
authors.initials: GY
authors.lastname: Rychkov
authors.forename: Michael B
authors.initials: MB
authors.lastname: Adams
authors.forename: Hans
authors.initials: H
authors.lastname: Holgert
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
authors.forename: Michael L
authors.initials: ML
authors.lastname: Roberts
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D019439:Chromaffin Cells / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011957:Receptors, Opioid / Q000819:agonists*; D012756:Sheep
chemical_list: D015220:Calcium Channels; D002395:Catecholamines; D009842:Oligopeptides; D015221:Potassium Channels; D011957:Receptors, Opioid; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; D020881:Enkephalin, D-Penicillamine (2,5)-; D002118:Calcium