PHARMACOLOGICAL MODULATION OF ADRENAL-MEDULLARY GABA(A) RECEPTOR - CONSISTENT WITH ITS SUBUNIT COMPOSITION

1 Muscimol, the specific GABA(A) receptor agonist, increased the secre tion of catecholamines by chromaffin cells with an EC(50) of 2.9+/-0.4 mu M 2 GABA(A) receptors of these cells were modulated by the same dr ugs which modulate GABA(A) receptors in brain tissue. 3 Benzodiazepine s enhanced muscimol-evoked catecholamine secretion by between 20 and 8 0%. This effect seems to be mediated by binding to a central type of b enzodiazepine receptor because it was completely blocked by the specif ic antagonist, Ro 15 1788. This antagonist was able to displace [H-3]- flunitrazepam binding with an EC(50) of 0.26+/-0.05 nM. 4 beta-Carboli nes weakly inhibited muscimol-induced catecholamine secretion and were able to displace [H-3]-flunitrazepam binding with an EC(50) between 0 .2 and 0.9 nM, depending on the beta-carboline used. 5 Pregnanolone an d related neuroactive steroids enhanced muscimol-evoked catecholamine secretion by up to 87%, in a dose-dependent fashion. In contrast pregn enolone weakly inhibited muscimol-evoked catecholamine secretion. 6 Zn 2+ did not affect GABA(A) receptor-induced catecholamine secretion. 7 These pharmacological results are absolutely concordant with the theor etical properties given by the GABA(A) receptor subunit composition of bovine adrenal medulla -alpha(1), alpha(4), beta(1-3), gamma(2)- prev iously characterized by Western blot analysis.