8-Bromo-cAMP mimics beta-adrenergic sensitization of GABA responses to ethanol in cerebellar Purkinje neurons in vivo.
Previous studies in our laboratory indicated that electrophysiological responses of cerebellar Purkinje neurons to GABA were not routinely potentiated by ethanol (EtOH), and the potentiation was not large when it occurred. In the presence of beta-adrenergic agonists, such as isoproterenol, however, GABA inhibitions became sensitive to potentiation by EtOH in nearly every Purkinje neuron tested. beta-adrenergic receptor activation alone also modulates (potentiates) GABA responses on Purkinje neurons, and this has been reported to be mediated by a cAMP second messenger system. Herein, we report that the membrane-permeable cAMP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), but not the membrane-impermeable cAMP, can also modulate GABA responses and that EtOH potentiates this facilitatory action of 8-Br-cAMP. These effects are not likely caused by adenosine receptor mechanisms, because this 8-bromoadenosine mediated modulation and sensitization was observed in the presence of systemic theophylline. These data suggest that the beta-adrenergic modulation and sensitization to EtOH of cerebellar Purkinje neuron GABA responses occur via a cAMP second messenger mechanism.
Freund
R K
RK
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Palmer
M R
MR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid