GABA_A Receptor Sites Modulating Catecholamine Secretion in the Rat Adrenal Gland: Evidence from ³H-Muscimol Autoradiography and in vivo Functional Studies

Abstract

The occurrence and distribution of specific ³H-muscimol binding sites, most probably identical with A type gamma-aminobutyric acid (GABA) receptors, were studied in sections of the rat adrenal gland by light microscope autoradiography. Specific binding was found primarily in the adrenal medulla, in association with chromaffïn cells. A limited number of binding sites was also observed within the adrenal cortex. In urethane-anaesthetized hexamethonium-pretreated rats, intravenous GABA produced a set of ‘excitatory’ cardiovascular effects (increase in heart rate, force of contraction and blood pressure) which were mimicked by intravenous muscimol but not by intravenous baclofen, and were antagonized by pretreatment with bicuculline. The cardiovascular excitatory effects of intravenous GABA were unaffected by reserpine pretreatment, markedly reduced by administration of phentolamine plus propranolol, and almost completely abolished by adrenalectomy. Our findings indicate the presence of GABA receptor sites on adrenal chromaffin cells, whose excitation can produce changes in cardiovascular function.

Drug-induced HPA axis alterations during acute critical illness: a multivariable association study

“…However, no effect on plasma ACTH could be demonstrated in the current study, which is not in favour of a central effect of propofol. However, GABA‐A‐receptor sites have been reported in rat adrenal chromaffin cells which modulate catecholamine secretion whereby indirectly cortisol secretion could be affected in this complex microenvironment. The GABA‐A‐receptor has also been described in bovine glomerulosa cells of the adrenal cortex, which mediate an inhibition of aldosterone secretion .…”

Role of Cl–Co-Transporters in the Excitation Produced by GABAAReceptors in Juvenile Bovine Adrenal Chromaffin Cells

“…Here we describe the molecular mechanism by which GABA produces excitation of adrenal chromaffin cells. Several lines of evidence suggest that GABA may play an important role in the physiology of the adrenal medulla; chromaffin cells possess the enzymes that synthesize and degrade GABA (Fernandez-Ramil et al 1983;Kataoka et al 1984); GABA is taken up by chromaffin cells and released in response to depolarizing stimuli (Kataoka et al 1984;Oset Gasque et al 1985, 1990; GABA immunoreactive nerve fibers are found throughout the adrenal medulla (Kataoka et al 1986;Oomori et al 1993) and bundles of GABA immunoreactive nerve fibers run into the medulla with varicosities often in close contact with chromaffin cells (Kataoka et al 1986;Oomori et al 1993); chromaffin cells express GABA A receptors (Amenta et al 1988;Bormann and Clapham 1985;Peters et al 1989); and immunoblots indicate the presence of ␣1, ␣4, ␤1-3, and ␥2 subunits (Parramon et al 1995a). Functionally it has been shown that GABA can elicit catecholamine release from isolated perfused adrenal glands (Fujimoto et al 1987;Gonzalez et al 1992;Kataoka et al 1984;Kitayama et al 1984;Sangiah et al 1974).…”

“…GABA immunoreactive nerve fibers are found throughout the adrenal medulla (Kataoka et al 1986;Oomori et al 1993). Chromaffin cells are known to express functional GABA A receptors with properties similar to their neuronal counterparts (Amenta et al 1988;Bormann and Clapham 1985). Sangiah et al (1974) first showed that GABA could elicit catecholamine release from isolated perfused adrenal glands, a result that has been repeated (Fujimoto et al 1987;Kataoka et al 1984;Kitayama et al 1984).…”

Etomidate elevates intracellular calcium levels and promotes catecholamine secretion in bovine chromaffin cells

“…GABA plays an important role in the physiology of the adrenal medulla: (1) chromaffin cells possess the enzymes that synthesize and degrade GABA (Fernandez‐Ramil et al 1983; Kataoka et al 1984); (2) GABA is taken up by chromaffin cells and released in response to depolarizing stimuli (Kataoka et al 1984; Oset Gasque et al 1985, 1990); (3) GABA‐immunoreactive nerve fibres are found throughout the adrenal medulla (Kataoka et al 1986; Oomori et al 1993) and bundles of GABA immunoreactive nerve fibres run into the medulla with varicosities often in close contact with chromaffin cells (Kataoka et al 1986; Oomori et al 1993); and (4) chromaffin cells express GABA A receptors (Bormann & Clapham, 1985; Amenta et al 1988; Peters et al 1989). Functionally it has been shown that GABA can elicit catecholamine release from isolated perfused adrenal glands (Sangiah et al 1974; Kataoka et al 1984; Kitayama et al 1984; Fujimoto et al 1987; Gonzalez et al 1992).…”