GABA_A and GABA_B receptors are functionally active in the regulation of catecholamine secretion by bovine chromaffin cells

Abstract

GABA stimulates the basal catecholamine release from adrenal bovine chromaffin cells in a calcium-dependent manner. This release represents about 70% of that obtained by similar doses of nicotine under similar experimental conditions. This effect is mediated by GABAA receptor sites present in chromaffin cells, since it was mimicked by muscimol and reversed by bicuculline. In addition, GABA, through its GABAA receptors, increases the catecholamine release evoked by submaximal doses of nicotine, but it has no effect on nicotine-evoked secretion of catecholamines when nicotine was given at maximal doses. These results seem to indicate that both nicotine and GABA release catecholamines from the same intracellular pool. In contrast, baclofen, a GABAB receptor agonist, depressed both basal and nicotine-evoked catecholamine release; this result indicates that in addition to GABAA control of catecholamine secretion by chromaffin cells, there is a GABAB control of this function. These results support the existence of a dual regulation of catecholamine secretion by both the GABAA and GABAB receptors in a similar way as that proposed for muscarinic and nicotinic cholinergic receptors.

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

“…The function of GABAA receptors has been clearly established (Kataoka et al, 1986;Kitayama et al, 1986;Castro et al, 1989). It is known that stimulation of cells by GABAA agonists depolarizes the chromaffin cell membrane producing an increase in Cl-efflux through the Cl-channel associated with the GABAA receptor and as a consequence, a membrane depolarization which culminates in an increase in basal catecholamine secretion (Gonzalez et al, 1992).…”

“…These include muscarinic cholinoceptors (Cheek & Burgoyne, 1985), opioid peptide (Lemaire et al, 1981), substance P (Livett et al, 1979), bradykinin (Owen et al, 1989), histamine HI (Chaliss et al, 1991), dopamine DI and D2 (Stauderman & Pruss, 1990;Huettl et al, 1991), prostaglandin E2 (Negishi et al, 1989;Ito et al, 1991), adenosine (Chern et al, 1988), angiotensin II (Marley et al, 1989;O'Sullivan & Burgoyne, 1989) and GABAA receptors (Castro et al, 1989).…”

Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits chromaffin cell secretion.

“…In some experiments, catecholamine release was measured electrochemically in a perfusion monitoring system (12)(13)(14). Freshly isolated chromaffin cells, purified and washed as described previously (9), were suspended in Locke's solution.…”

“…Cells were then stimulated with pulses of 250 j.M DMPP+. Released catecholamines were measured directly by an electrochemical detector (Metrohm model 641-VA) as described (12). None of the drugs produced electrochemical signals interfering with catecholamine detection.…”

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).…”