Chronic exposure of neonatal rat adrenomedullary chromaffin cells to opioids in vitro blunts both hypoxia and hypercapnia chemosensitivity.
J Physiol
; 591(2): 515-29, 2013 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-23148319
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 â¼1 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glândulas Suprarrenais
/
Células Cromafins
/
Analgésicos Opioides
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article