title: Opioid modulation of calcium current in cultured sensory neurons: mu-modulation of baroreceptor input.
abstract: We used the whole cell open-patch or perforated-patch technique to characterize mu-opioid modulation of Ca(2+) current (I(Ca)) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The mu-opiate receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I(Ca) in 95% of neonatal [postnatal day (P)1-P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20-P35) and 61% of adult cells (P60-P110) responded to DAGO. DAGO-mediated inhibition of I(Ca) was naloxone sensitive, irreversible in the presence of guanosine 5'-O-(3-thiotriphosphate), absent with guanosine 5'-O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO's inhibition of I(Ca) was G protein mediated. Incubation of neurons with omega-conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of omega-conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC(50) of 1.82 x 10(-8) M. DAGO slowed activation of I(Ca), but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, mu-opiate modulation of I(Ca) in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of mu-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii.
authors.affiliation: Division of Pediatric Cardiology and Molecular Physiology and Biophysics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hamra
authors.forename: R S
authors.initials: RS
authors.lastname: McNeil
authors.forename: M
authors.initials: M
authors.lastname: Runciman
authors.forename: D L
authors.initials: DL
authors.lastname: Kunze
mesh_terms: D000375:Aging / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D004553:Electric Conductivity; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017450:Receptors, Opioid, mu / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D015220:Calcium Channels; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D019204:GTP-Binding Proteins; D002118:Calcium