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Activation of alpha 1-adrenergic receptors in slices of rat brain increases inositol phosphate accumulation, increases basal cyclic AMP accumulation, and potentiates the increase in cyclic AMP caused by adenosine. We compared these three responses to determine whether they are mediated by the same receptors. The increase in inositol phosphates and the potentiation of cyclic AMP accumulation in cerebral cortex were largely blocked by chelation of extracellular calcium, whereas the increase in basal cyclic AMP was not affected. The magnitude of the increase in inositol phosphates in different brain regions correlated with the magnitude of the potentiation of cyclic AMP accumulation (r = 0.80), but neither of these correlated with the magnitude of the increase in basal cyclic AMP. Although other alkylating agents inactivated all of the alpha 1-adrenergic receptor-binding sites labeled with 125IBE 2254 in membrane preparations of cerebral cortex, chlorethylclonidine (CEC) potently and selectively inactivated only half of these sites. Pretreatment with CEC partially blocked the increase in basal cyclic AMP, but not the increase in inositol phosphates or potentiation of cyclic AMP accumulation in slices of cerebral cortex. Comparing different brain regions, there was a better correlation between the density of 125IBE 2254-binding sites not inactivated by CEC with the magnitude of the increase in inositol phosphates or potentiation of cyclic AMP accumulation than with the increase in basal cyclic AMP. Although the largest increase in inositol phosphates was observed in slices of hippocampus, there was only a small increase in basal cyclic AMP in this region, and CEC did not inactivate any 125IBE-binding sites in hippocampus. Phentolamine and WB 4101 were significantly more potent in inhibiting specific 125IBE 2254 binding in hippocampus than in cerebral cortex. After treatment of cerebral cortical membranes with CEC, however, these drugs had potencies similar to those observed in hippocampus. The results suggest that the alpha 1-adrenergic receptors mediating increases in basal cyclic AMP accumulation can be differentiated from those mediating increases in inositol phosphate accumulation and potentiating adenosine stimulated cyclic AMP accumulation by their binding properties, calcium dependency, regional distribution, and sensitivity to the alkylating agent CEC.
R D Johnson, and
K P Minneman
June 1986,
The Journal of pharmacology and experimental therapeutics,
R D Johnson, and
K P Minneman
February 1987,
Archives of biochemistry and biophysics,
R D Johnson, and
K P Minneman
December 1978,
Brain research,
R D Johnson, and
K P Minneman
November 1980,
Biochimica et biophysica acta,
R D Johnson, and
K P Minneman
July 1990,
Journal of neurochemistry,
R D Johnson, and
K P Minneman
April 1985,
European journal of pharmacology,
R D Johnson, and
K P Minneman
April 1990,
Biochemical and biophysical research communications,
R D Johnson, and
K P Minneman
September 1980,
Life sciences,
R D Johnson, and
K P Minneman
October 1986,
Brain research,
R D Johnson, and
K P Minneman
March 1983,
Molecular pharmacology,
