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Neuroendocrine -Aminobutyric Acid (GABA): Functional Differences in GABA_A Versus GABA_B Receptor Inhibition of the Melanotrope Cell of Xenopus laevis¹

Department of Cellular Animal Physiology, Nijmegen Institute for Neurosciences, Subfaculty of Biology, University of Nijmegen, Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Dr. B. G. Jenks, Department of Cellular Animal Physiology, Nijmegen Institute for Neurosciences, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. E-mail: Jenks{at}sci.kun.nl

The melanotrope cell of Xenopus laevis is innervated by nerve terminals that contain, among other transmitter substances, the neurotransmitter -aminobutyric acid (GABA). Postsynaptically the melanotrope cell possess both GABA_A and GABA_B receptors. Activation of either receptor type leads to an inhibition of MSH release from the cell. The present study concerns the functional significance of the existence of two types of GABA receptors on the melanotrope regarding two questions: 1) do the different receptor types have different effects on the melanotrope? and 2) can the endogenous ligand GABA differentially activate 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 negatively linked to adenylyl cyclase) may have differential effects on the sensitivity of the cell to stimulation by cAMP-dependent mechanisms. We show that treatments with either isoguvacine (GABA_A agonist) or baclofen (GABA_B agonist) inhibit intracellular Ca²⁺ oscillations and peptide secretion from melanotrope cells. Treatments known to increase intracellular 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 melanotrope cell by differentially affecting the sensitivity the cell shows to stimulation by cAMP-dependent mechanisms. Concerning possible differential activation of the receptor types, we found that we could use a membrane potential probe (from the bis-oxonol family) to differentiate between GABA_A and GABA_B receptor activation. Using this probe we showed that low GABA concentrations (<10^-7 M) give a response indicative of the GABA_B receptor, whereas at high GABA concentrations (>10^-7 M), the GABA_A receptor response predominates. We, therefore, conclude that GABA can differentially activate the two types of GABA receptors on the Xenopus melanotrope cell.

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