Characterization of the relationship between gamma-aminobutyric acid B agonists and transmitter-coupled cyclic nucleotide-generating systems in rat brain.
Baclofen and other gamma-aminobutyric acid B (GABAB) agonists potentiate the cyclic AMP response in rat brain slices that occurs during exposure to norepinephrine, isoproterenol, adenosine, vasoactive intestinal peptide, and histamine. By themselves the GABAB agonists have only a slight effect on basal cyclic AMP levels. Dose-response and time-course studies revealed that baclofen has little influence on neurotransmitter recognition site affinity, but rather enhances the synthesis or accumulation of second messenger that occurs in response to these agents. Baclofen appears to be neither an inhibitor of phosphodiesterases nor does it require adenosine to promote the response to other transmitters. The synergistic interaction between baclofen and catecholamines is a calcium-dependent process and is evident only in the rat brain cerebral cortex, hippocampus and corpus striatum, being undetectable in the pons-midbrain, cerebellum, and spinal cord. In contrast to the findings with neurotransmitter receptor stimulants, GABAB agonists inhibited the cyclic AMP response to forskolin. It remains unclear whether this action is related to the neurotransmitter potentiating effect of baclofen. These data suggest that GABAB agonists may modulate neurotransmitter receptor function by influencing a component of the cyclic nucleotide-generating system beyond the level of the hormone recognition site.
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D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D001418:Baclofen; D000241:Adenosine; D007545:Isoproterenol; D009638:Norepinephrine