Excitation of locus coeruleus neurons by vasoactive intestinal peptide: role of a cAMP and protein kinase A.
In accord with previous studies, it was found that vasoactive intestinal peptide (VIP), a powerful activator of adenylate cyclase, and cAMP-active agents (i.e., 8-Br-cAMP, forskolin, and Ro20-1724) increased the firing rate of noradrenergic neurons in the locus coeruleus (LC) by inducing an inward current. The response to VIP was usually more rapid and larger in a subpopulation of LC neurons with subthreshold rhythmic oscillations in membrane potential (oscillatory cells) as compared to nonoscillatory cells. In either case, the inward currents elicited by VIP and cAMP-active agents were found to be nonadditive, suggesting the action of VIP, at least in part, is via the same mechanism as that of cAMP-active agents. Intracellular application of a specific protein (or related peptide) inhibitor of cAMP-dependent protein kinase markedly attenuated the activation induced by either cAMP-active agents or VIP, suggesting that cAMP-dependent protein kinase (protein kinase A), presumably through protein phosphorylation, plays a role in the action of VIP. Taken together, the results provide evidence that cAMP and protein kinase A are involved in mediating the electrophysiological actions of VIP on LC neurons.
Wang
Y Y
YY
Department of Pharmacology, School of Medicine, Yale University, New Haven, Connecticut.
Aghajanian
G K
GK
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D047908:Intracellular Signaling Peptides and Proteins; D008125:Locus Coeruleus / Q000166:cytology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C015482:protein kinase modulator; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D011494:Protein Kinases