CHARACTERIZATION OF THE RELATIONSHIP BETWEEN GAMMA-AMINOBUTYRIC ACID-B AGONISTS AND TRANSMITTER-COUPLED CYCLIC NUCLEOTIDE-GENERATING SYSTEMS IN RAT-BRAIN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 27  (1) , 53-59
Abstract
Baclofen and other GABAB agonists potentiate the cAMP 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 cAMP 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 2nd 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 Ca2+-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 cAMP response to forskolin. It remains unclear whether this action is related to the neurotransmitter potentiating effect of baclofen. 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.