NEUROENDOCRINE GAMMA-AMINOBUTYRIC-ACID (GABA) - FUNCTIONAL DIFFERENCES IN GABA(A) VERSUS GABA(B) RECEPTOR INHIBITION OF THE MELANOTROPE CELL OF XENOPUS-LAEVIS

The melanotrope cell of Xenopus laevis is innervated by nerve terminal s that contain, among other transmitter substances, the neurotransmitt er gamma-aminobutyric acid (GABA). Postsynaptically the melanotrope ce ll possess both GABA(A) and GABA(B) receptors. Activation of either re ceptor type leads to an inhibition of alpha MSH release from the cell. The present study concerns the functional significance of the existen ce of two types of GABA receptors on the melanotrope regarding two que stions: 1) do the different receptor types have different effects on t he melanotrope? and 2) can the endogenous ligand GABA differentially a ctivate these receptors? Concerning the first question, we have tested the hypothesis that the GABA(A) receptor(a chloride ion channel) and the GABA(B) receptor (a G protein-coupled receptor neg negatively link ed to adenylyl cyclase) may have differential effects on the sensitivi ty of the cell to stimulation by cAMP-dependent mechanisms. We show th at treatments with either isoguvacine (GABA(A) agonist) or baclofen (G ABA(B) agonist) inhibit intracellular Ca2+ oscillations and peptide se cretion from melanotrope cells. Treatments known to increase intracell ular cAMP in the melanotrope (e.g. use of the peptide sauvagine or the cAMP analog 8-bromo-cAMP) completely overcame the inhibition induced by baclofen, but not that caused by isoguvacine. We conclude that the GABA(A) and GABA(B) receptors have different effects on the Xenopus me lanotrope cell by differentially affecting the sensitivity the cell sh ows to stimulation by cAMP-dependent mechanisms. Concerning possible d ifferential activation of the receptor types, we found that we could u se a membrane potential probe (from the bis-oxonol family) to differen tiate between GABA(A) and GABA(B) receptor activation. Using this prob e we showed that low GABA concentrations (< 10(-7) M) give a response indicative of the GABA(B) receptor, whereas at high GABA concentration s (> 10(-7) hr), the GABA(A) receptor response predominates. We, there fore, conclude that GABA can differentially activate the two types of GABA receptors on the Xenopus melanotrope cell.