title: Chronic exposure of neonatal rat adrenomedullary chromaffin cells to opioids in vitro blunts both hypoxia and hypercapnia chemosensitivity.
abstract: At birth, rat adrenomedullary chromaffin cells (AMCs) respond directly to asphyxial stressors such as hypoxia and hypercapnia by triggering catecholamine secretion, which is critical for proper transition to extrauterine life. These non-neurogenic responses are suppressed postnatally in parallel with the development of splanchnic innervation, and reappear following denervation of the adult adrenal gland. To test whether neural factors released from the splanchnic nerve may regulate AMC chemosensitivity, we previously showed that nicotinic agonists in utero and in vitro suppressed hypoxia, but not hypercapnia, sensitivity. Here, we considered the potential role of opiate peptides which are also released from the splanchnic nerve and act via postsynaptic μ-, δ- and -opioid receptors. Treatment of neonatal rat AMC cultures for ∼1 week with μ- and/or δ- (but not ) opioid agonists (2 μm) led to a marked suppression of both hypoxia and hypercapnia sensitivity, as measured by K(+) current inhibition and membrane depolarization; co-incubation with naloxone prevented the effects of combined opioids. The suppression of hypoxia sensitivity was attributable to upregulation of K(ATP) current density and the K(ATP) channel subunit Kir6.2, and was reversed by the K(ATP) channel blocker, glibenclamide. By contrast, suppression of hypercapnia sensitivity was associated with down-regulation of two key mediators of CO(2) sensing, i.e. carbonic anhydrase I and II. Collectively, these studies point to a novel role for opioid receptor signalling in the developmental regulation of chromaffin cell chemosensitivity, and suggest that prenatal exposure to opioid drugs could lead to impaired arousal responses in the neonate.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Shaima
authors.initials: S
authors.lastname: Salman
authors.forename: Josef
authors.initials: J
authors.lastname: Buttigieg
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Colin A
authors.initials: CA
authors.lastname: Nurse
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000311:Adrenal Glands / Q000166:cytology* / Q000294:innervation; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013153:Splanchnic Nerves / Q000502:physiology; D000099161:Kcnj11 Channel
chemical_list: D000701:Analgesics, Opioid; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D005905:Glyburide; D054086:KATP Channels; D009270:Naloxone; D009292:Narcotic Antagonists; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011957:Receptors, Opioid; D000099161:Kcnj11 Channel