Regulation of Neurotransmitter Responses in the Central Nervous System

Abstract : Gamma-Aminobutyric acid (GABA) is a key inhibitory neurotransmitter in the mammalian central nervous system. Two major categories of receptors, termed GABA(A) and GABA(B) are activated by the amino acid. Whereas GABA(A) receptors appear to be directly involved in synaptic transmission, GABA(B) receptors may function as neuromodulatory sites. Baclofen (BAC), a GABA(B) agonist has been shown to have multiple effects on stimulus-evoked increases in second messenger production. For example, BAC augments cAMP formation in the presence of catecholamines but inhibits the response evoked by the direct adenylate cyclase activator, forskolin. Results from the current study have demonstrated the presence of these GABA(B) effects in several mammalian species suggesting a broad physiological relevance. Using a variety of different pharmacophores, evidence is presented supporting the notion that the augmenting and inhibitory efforts of GABA(B) agonists are mediated through pharmacologically distinct reports. Finally, the augmenting response does not appear to be mediated through protein kinase C. However, BAC may facilitate second messenger production by alerting the coupling of catecholamine receptor to G-proteins involved in the cAMP cascade.