A dopaminergic receptor modulates catecholamine release from the cat adrenal gland

Nicotine evokes the release of catecholamines from perfused cat adrenal glands in a concentration-dependent manner, the median effective concentration for nicotine being 5 microM. Two 2 min pulses of 5 microM-nicotine, 40 min apart (S1 and S2) gave net catecholamine outputs of 7.64 and 3.55 micrograms/8 min, respectively. The ratio S2/S1 in control glands was 0.5. Increasing concentrations of apomorphine (1-10 microM) markedly inhibited catecholamine release during the second nicotine pulse (S2). At 1 microM-apomorphine, the release during S2 was significantly reduced to 16% of S1; with 10 microM-apomorphine, the secretory response was reduced further to only 3% of S1, the ratio S2/S1 being 0.03. The presence of haloperidol, sulpiride or picobenzide (each 0.5 microM) during S2, completely reversed the inhibition of catecholamine release produced by apomorphine. Haloperidol itself increased the nicotinic secretory response during S2; so, while the ratio S2/S1 was 0.5 in control conditions, this ratio increased significantly to 0.95 if haloperidol (0.5 microM) was present during S2, suggesting that the presence of this dopaminergic antagonist removed a negative feed-back mechanism that inhibits nicotine-evoked catecholamine release. If present during S2, dopamine (1 microM) also markedly inhibited catecholamine release evoked by nicotine; this inhibition was again reversed by 0.5 microM-haloperidol. Neither the opiate antagonist naloxone nor the alpha-adrenoceptor blocking agent phentolamine (at concentrations of 0.5-5 microM) affected the inhibition by apomorphine of the secretory response to nicotine. These data strongly suggest that the cat adrenal medulla chromaffin cell membrane contains a dopaminergic receptor which modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. The fact that dopamine is released in measurable amounts, together with adrenaline and noradrenaline, from perfused cat adrenal glands in response to nicotinic stimulation (V. Ceña, unpublished results), favours a role for this dopaminergic receptor in modulating catecholamine release from the chromaffin cell.