Regulation of alpha-1 adrenergic receptor density and functional responsiveness in rat brain.
The effects of changes in norepinephrine availability on alpha-1 adrenergic receptor density and responsiveness were determined in several regions of rat brain. Receptor density was determined from specific 125I-BE 2254 binding, and responsiveness was determined by norepinephrine-stimulated increases in inositol phosphate accumulation and in cyclic AMP accumulation in the absence or presence of adenosine in slices where beta adrenergic receptors had been inactivated. Adrenergic input was reduced by destroying noradrenergic neurons with DSP-4, depleting amines with chronic reserpine treatment or blocking alpha-1 adrenergic receptors with chronic prazosin treatment. All three treatments caused similar increases in alpha-1 adrenergic receptor density in cerebral cortex but not in striatum or hippocampus. DSP-4 treatment increased the maximal cyclic AMP response to both norepinephrine and phenylephrine but did not alter the maximal inositol phosphate response or the maximal potentiation of the cyclic AMP response to adenosine. DSP-4 treatment also increased the potency of norepinephrine in activating all three responses in cerebral cortex. Adrenergic input was increased by chronic treatment with desmethylimipramine to block norepinephrine reuptake, chronic i.c.v. infusion of norepinephrine or chronic yohimbine treatment to block presynaptic autoreceptors. None of these treatments caused significant changes in alpha-1 adrenergic receptor density or functional responsiveness in any region studied. The results suggest that alpha-1 adrenergic receptor density and responsiveness in rat brain can be increased but not easily decreased. They also suggest that different brain regions are affected differently by alterations of adrenergic input and that the different responses are not coregulated.
Johnson
R D
RD
Department of Pharmacology, Emory University Medical School, Atlanta, Georgia.
Iuvone
P M
PM
Minneman
K P
KP
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D001596:Benzylamines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012110:Reserpine; D000242:Cyclic AMP; C012102:DSP 4; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin