Metabotropic glutamate receptors limit adenylyl cyclase-mediated effects in rat hippocampus via protein kinase C.
Glutamate receptors of the metabotropic type (mGluRs) activate protein kinase C in hippocampus, but few physiological functions of this pathway are known. The present data show that mGluRs utilize protein kinase C to inhibit another second messenger system, the adenylyl cyclase pathway, in neurons of the CA1 area of hippocampus. Activation of mGluRs prevented beta-adrenergic receptors, which couple to adenylyl cyclase, from blocking the slow Ca2+-dependent afterhyperpolarization (AHP). Since the afterhyperpolarization modulates neuronal responsiveness, crosstalk between protein kinase C and the adenylyl cyclase pathway is likely to have physiological consequences. Moreover, mGluRs themselves block the afterhyperpolarization, so the observed interference with the beta-adrenergic response constitutes a hierarchical relationship in which mGluRs are dominant over beta-adrenergic receptors.
Nouranifar
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R
Psychiatry Service, Bronx Veterans Administration Medical Center, NY 10468, USA.
Blitzer
R D
RD
Wong
T
T
Landau
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E
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D015290:Second Messenger Systems
D011943:Receptors, Adrenergic, beta; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol