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Direct Effects of Chronic Ethanol Exposure on β ‐Adrenergic and Adenosine‐Sensitive Adenylate Cyclase Activities and Cyclic AMP Content in Primary Cerebellar Cultures
Author(s) -
Rabin Richard A.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb08829.x
Subject(s) - adenylate kinase , cyclase , adenosine , medicine , endocrinology , chemistry , ethanol , stimulation , norepinephrine , biochemistry , receptor , biology , dopamine
The direct effects of chronic ethanol exposure on adenylate cyclase activity and cyclic AMP content were investigated in primary cerebellar cultures. By morphological criteria these cultures mainly contain granule cells with some astrocytes, and each cell type appears to contain both β ‐adrenergic and adenosine‐sensitive adenylate cyclase systems. Chronic treatment of the primary cerebellar cultures with 120 m M ethanol for 6 days caused a reduction in the stimulation of cyclic AMP content by isoproterenol and by the adenosine analogue 2‐chloroadenosine. Kinetic analysis indicated that the chronic ethanol treatment decreased maximal activation of adenylate cyclase, as well as increased the EC 50 values for norepinephrine and 2‐chloroadenosine. Activation of norepinephrine‐stimulated adenylate cyclase activity by in vitro ethanol was significantly enhanced after the chronic ethanol exposure. However, the chronic treatment did not alter activation of the 2‐chloroadenosine‐stimulated enzyme by in vitro ethanol. A similar difference in the response to in vitro ethanol after the chronic treatment was observed when cyclic AMP content of the intact cells was measured. The present data indicate that chronic ethanol exposure causes a selective increase in the sensitivity of adenylate cyclase to ethanol in some brain cells and a more generalized desensitization of receptor‐stimulated cyclic AMP production.