Common alpha 2- and opiate effector mechanisms in the locus coeruleus: intracellular studies in brain slices.
Although alpha 2-adrenoceptor and opiate agonists act through separate receptors on neurons in the locus coeruleus (LC), there are several lines of evidence pointing to shared post-receptor effector mechanisms. Stimulation of either alpha 2- and opiate receptors causes a hyperpolarization of neurons in the locus coeruleus; this effect is due, at least partly, to an opening of a common set of K+ channels. Moreover, the alpha 2- and opiate receptor-induced hyperpolarizations are both reversed, at least partially, by membrane-permeable analogs of adenosine 3':5'-monophosphate (cAMP). These findings fit with biochemical models which propose that alpha 2- and opiate receptors have common actions through inhibiting adenylate cyclase through the inhibitory guanosine triphosphate (GTP) binding protein (Gi). As would be predicted by this model, pretreatment with pertussis toxin, an inactivator of Gi, blocks the hyperpolarizing effects of alpha 2- and opiate agonists in the locus coeruleus. These results suggest that the electrophysiological effects, mediated by these receptors, are transduced through Gi (or a closely related G protein). However, new evidence indicates that there may be both cAMP-dependent and cAMP-independent actions, mediated through G proteins. The opening of K+ channels by alpha 2- and opiate receptors appears to be independent of cAMP, whereas a cAMP-dependent inward current (IcAMP) would be affected by the inhibition of adenylate cyclase; these two G protein-mediated events work in concert to produce the alpha 2- and opiate hyperpolarization of neurons in the locus coeruleus.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology; D008125:Locus Coeruleus / Q000378:metabolism*; D008564:Membrane Potentials; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007473:Ion Channels; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009020:Morphine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D003000:Clonidine; D011188:Potassium