Selective mu and kappa Opioid Agonists Inhibit Voltage-Gated Ca2+ Entry in Isolated Neonatal Rat Carotid Body Type I Cells
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 860)
It is known that opioids inhibit the hypoxic ventilatory response in part via an action at the carotid body, but little is known about the cellular mechanisms that underpin this. This study’s objectives were to examine which opioid receptors are located on the oxygen-sensing carotid body type I cells from the rat and determine the mechanism by which opioids might inhibit cellular excitability.
Immunocytochemistry revealed the presence of μ and κ opioid receptors on type I cells. The μ-selective agonist DAMGO (10 μM) and the κ-selective agonist U50-488 (10 μM) inhibited high K+ induced rises in intracellular Ca2+ compared with controls. After 3 h incubation (37 °C) with pertussis toxin (150 ng ml−1), DAMGO (10 μM) and U50-488 (10 μM) had no significant effect on the Ca2+ response to high K+.
These results indicate that opioids acting at μ and κ receptors inhibit voltage-gated Ca2+ influx in rat carotid body type I cells via Gi-coupled mechanisms. This mechanism may contribute to opioid’s inhibitory actions in the carotid body.
KeywordsCarotid body Type I cells Opioid receptors Ca2+ imaging
Burlon DC, Jordan HL, Wyatt CN (2009) Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine. Respir Physiol Neurobiol 168(3):218–223PubMedCrossRefGoogle Scholar
eSilva MJM, Lewis DL (1995) L- and N-type Ca2+
channels in adult carotid body chemoreceptor type I cells. J Physiol 489(3):689–699CrossRefGoogle Scholar
Feng Y, He X, Yang Y, Chao D, Lazarus L, Xia Y (2012) Current research on opioid receptor function. Curr Drug Targets 13(2):230–246PubMedCrossRefPubMedCentralGoogle Scholar
Greer JJ, Carter JE, Al-Zubaidy Z (1995) Opioid depression of respiration in neonatal rats. J Physiol 485(3):845–855PubMedCrossRefPubMedCentralGoogle Scholar
Kirby GC, McQueen DS (1986) Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. Br J Pharmacol 88:889–898PubMedCrossRefPubMedCentralGoogle Scholar
Lalley PM (2003) Mu-opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbances. Am J Physiol Regul Integr Comp Physiol 285:1287–1304CrossRefGoogle Scholar
Mansour A, Watson SJ (1993) Anatomical distribution of opioid receptors in mammalians: an overview. Handb Exp Pharmacol 104:79–105CrossRefGoogle Scholar
Mayer N, Zimpfer M, Raberger G, Beck A (1989) Fentanyl inhibits canine carotid chemoreceptor reflex. Anesth Analg 69:756–762PubMedCrossRefGoogle Scholar
Mutolo D, Bongianni F, Einum J, Dubuc R, Pantaleo T (2007) Opioid-induced depression in the lamprey respiratory network. Neuroscience 150:720–729PubMedCrossRefGoogle Scholar
Zhang Z, Zhuang J, Zhang C, Xu F (2011) Activation of opioid μ-receptors in the commissural subdivision of the nucleus tractus solitarius abolishes the ventilatory response to hypoxia in anesthetized rats. Anesthesiology 115(2):353–363PubMedCrossRefGoogle Scholar
© Springer International Publishing Switzerland 2015