Systemic phenoxybenzamine but not beta-adrenergic antagonists block noradrenergic inhibition of cerebellar Purkinje and hippocampal pyramidal neurons.
Previous pharmacological characterization of central noradrenergic receptors has been interpreted as favoring beta-type receptors on cerebellar Purkinje neurons and hippocampal pyramidal neurons. However, the recent development of additional noradrenergic antagonists suitable for single neuron analysis, prompted an initial re-evaluation of alpha and beta adrenergic receptors in these two cell populations. In contrast with earlier data based on local antagonism of iontophoretric or synaptically released norepinephrine (NE), we now find that systemic phenoxybenzamine, the alpha antagonist, was effective in blocking responses to NE in cerebellum and hippocampus, whereas systemic beta antagonists metoprolol, ICI 118.551 [correction of ICI 181.551], or proprandol did not interfere with local NE responses at systemic doses that altered spontaneous discharge rates. These preliminary data suggest that a more complete re-evaluation of the nature of central noradrenergic response mechanisms may be warranted.
Staunton
D A
DA
Scripps Clinic Research Foundation, La Jolla, California.
Svensson
T H
TH
Chouvet
G E
GE
Siggins
G R
GR
Bloom
F E
FE
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; C026777:ICI 118551; D005680:gamma-Aminobutyric Acid; D011433:Propranolol; D008790:Metoprolol; D009638:Norepinephrine