GABA_A and GABA_B sites in bovine adrenal medulla membranes

Abstract

The effect of several ligands and Ca2+ ions on [3H]GABA binding to bovine adrenal medulla membranes was investigated. Without any blockade, the [3H]GABA binding showed two components, one of low affinity (Kd = 139 +/- 22 nM and Bmax = 3.2 +/- 0.4 pmol/mg protein) and the other of high affinity (Kd = 41 +/- 6 nM and Bmax = 0.35 +/- 0.26 pmol/mg protein). Muscimol specifically blocked low-affinity sites, and (-)baclofen blocked high-affinity components. Ca2+ ions were strictly necessary for maximum binding to high-affinity sites, whereas they did not significantly affect sites of the lower affinity. These results show that the bovine adrenal medulla has a GABAA receptor population of low affinity together with a GABAB receptor of high affinity.

GABAB receptors modulate catecholamine secretion in chromaffin cells by a mechanism involving cyclic AMP formation

“…However they are of the same order of magnitude as those required to stimulate GABAB responses in other peripheral tissues such as the inhibition of ileum peristalsis or inhibition of glutamate, acetylcholine and noradrenaline release in the peripheral nervous system (100-300 gM), although in all these cases GABAB responses were inhibitory. These findings together with the fact that GABAB responses on chromaffin cell catecholamine secretion represent between 40-50% of those obtained with nicotine at the same doses, seem to suggest either a low affinity of GABAB receptors or the existence of a low number of GABAB binding sites in adrenal medullary cells (Castro et al, 1988).…”

“…GABA has two binding sites in the adrenal medulla, characterized as GABAA and GABAB receptors because of their capacity to be blocked with saturating concentrations of muscimol or baclofen, respectively and their sensitivity to Ca2" ions (Castro et al, 1988). The function of GABAA receptors has been clearly established (Kataoka et al, 1986;Kitayama et al, 1986;Castro et al, 1989).…”

“…Moreover, the presence of the two subtypes of GABA receptors, one sensitive to muscimol (GABAA) and the other insensitive to muscimol but sensitive to baclofen (GABAB) has also been described (Castro et al, 1988).…”

Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

“…Many substances, including opioid peptides, substance P. y-aminobutyric acid and peptides derived from cromogranin A, appear to modulate acetylcholine-mediated catecholamine (CA) release from these cells (Mizobe et al, 1979;Kumakura et al, 1980;Castro et al, 1988;Simon et al, 1988).…”

Pharmacological modulation of adrenal medullary GABAA receptor: consistent with its subunit composition

“…This is the case with the adrenal medulla, where GABA regulates catecholamine (CA) secretion (Castro et al, 1989). This function is mainly mediated by binding to GABAA receptors (Kataoka et al, 1984;Castro et al, 1988), through a mechanism dependent on the membrane potential (Gonzalez et al, 1992).…”