title: Efficacy and kinetics of opioid action on acutely dissociated neurons.
abstract: Opioids have been shown to cause a potent inhibition of neurons in the locus ceruleus (LC) in vivo in brain slices and isolated neurons; however, the kinetics of opioid action have not been described. In this study, we used acutely isolated LC neurons to examine opioid and alpha2-adrenoceptor action on potassium and calcium currents. [Met]Enkephalin (ME), [D-Ser2,Leu5,Thr6]-enkephalin, etorphine, and [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin increased potassium conductance, whereas morphine and naloxone were antagonists. The time constant of potassium channel activation was approximately 0.7 sec and was the same for each agonist. The amplitude of the current and the time constant of decay were dependent on the agonist, suggesting that agonist efficacy and affinity, respectively, determined these parameters. The amplitude of potassium current induced by the alpha2-adrenoceptor agonist UK14304 was not significantly different from that induced by ME, but the time constant of current activation was half that of ME, and the decline was more rapid. When potassium conductances were blocked with the combination of internal cesium and external barium, opioid and alpha2 agonists had no effect at potentials more negative than -50 mV and decreased barium currents at potentials between -40 and +20 mV. Both morphine and clonidine caused a small inhibition of barium current. In dorsal root ganglion cells, morphine alone had small and inconsistent effects on the calcium current, but it always competitively antagonized the inhibition caused by [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin. The results in isolated LC neurons suggest 1) the amplitude and time course of the opioid-induced potassium current depend on agonist efficacy and affinity and 2) the coupling of both mu-opioid and alpha2-adrenoceptors to calcium channels seems to be more efficient than that to potassium channels.
authors.affiliation: The Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ingram
authors.forename: T J
authors.initials: TJ
authors.lastname: Wilding
authors.forename: E W
authors.initials: EW
authors.lastname: McCleskey
authors.forename: J T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000818:Animals; D000068438:Brimonidine Tartrate; D015220:Calcium Channels / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D004745:Enkephalins; D009294:Narcotics; D015221:Potassium Channels; D011810:Quinoxalines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005048:Etorphine; D000068438:Brimonidine Tartrate; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D009020:Morphine; D003000:Clonidine