Electrophysiological effects of locally applied noradrenergic agents at cerebellar Purkinje neurons: receptor specificity.
We have investigated the receptor subtype(s) mediating the noradrenergic inhibition of cerebellar Purkinje cell spontaneous firing rate using local application of specific agonists and antagonists, in situ, via pressure microejection. Extracellular action potentials were recorded from Purkinje neurons in anesthetized Fischer 344 rats. Timolol, a beta-receptor antagonist, did not affect norepinephrine (NE)-induced inhibition in 9 of 12 cells studied. Phentolamine, an alpha-receptor antagonist, blocked the effect of NE in 8 of 11 cells. To further determine the subtype of alpha-receptor involved, the effects of the alpha 1-antagonist prazosin and alpha 2-antagonists idazoxan and yohimbine were examined. While prazosin had no effect on NE-mediated inhibition, both idazoxan and yohimbine blocked NE effects. Idazoxan was also successful in blocking phencyclidine (PCP), an indirect noradrenergic agonist. The inhibitory action of NE upon Purkinje cell firing rate was mimicked by the selective alpha 2-agonist clonidine; this action of clonidine was blocked by idazoxan but not by timolol or prazosin. In addition, the alpha 1-adrenergic agonist phenylephrine and the beta-adrenergic agonist isoproterenol inhibited Purkinje cell firing rate. Phenylephrine effects were blocked by prazosin but not by timolol or idazoxan. Isoproterenol-induced inhibition was blocked by timolol but not phentolamine. Taken together, these studies suggest that both alpha- and beta-receptors alter Purkinje cell firing rate; the depressant action of locally applied NE, however, seems to be mediated primarily via an alpha 2-adrenergic receptor.
Parfitt
K D
KD
Department of Pharmacology, University of Colorado Health Sciences, Denver 80262.
Freedman
R
R
Bickford-Wimer
P C
PC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D019329:Idazoxan; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology*
D004146:Dioxanes; D004147:Dioxins; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D010622:Phencyclidine; D009638:Norepinephrine; D019329:Idazoxan; D010646:Phentolamine