Dopamine Receptors on Adrenal Chromaffin Cells Modulate Calcium Uptake and Catecholamine Release

Abstract

The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

Modulation of secretion by dopamine involves decreases in calcium and nicotinic currents in bovine chromaffin cells.

“…Dopaminergic agonists were shown to inhibit secretion of adrenaline and noradrenaline from perfused adrenal glands (Artalejo, Garcia, Montiel & Sanchez-Garcia, 1985; Gonzalez, Artalejo, Montiel, Hervas & Garcia, 1986) and from chromaffin cells maintained in primary culture (Bigornia, Suozzo, Ryan, Napp & Schneider, 1988). The reversal of the inhibitory effects of dopamine by specific D2 antagonists suggests that the effects are mediated by a D2 receptor in the adrenal medulla and the presence of D2 but not D1 dopamine receptors was demonstrated in ligand binding studies on chromaffin cell membrane suspensions (Gonzales et al 1986;Lyon, Titeler, Bigornia & Schneider, 1987;Quick, Bergeron, Mount & Philie, 1987).…”

“…While earlier work demonstrated that dopamine inhibited nicotinic-evoked catecholamine release (Artalejo et al 1985), more recent data suggest that dopamine decreases secretion from adrenal chromaffin cells by altering Ca2+ channel conductance (Bigornia et al 1988). To assess the possible role of voltage-gated Ca2+ channels and of acetylcholine-activated channels in the dopamine-induced inhibition of catecholamine release, we have compared the effect of D2 agonists on Ca2+ and Na+ uptake evoked by different secretagogues.…”

Heterologous Expression of the Human D2S Dopamine Receptor in Protease‐Deficient Saccharomyces cerevisiae Strains

“…It exists in two isoforms (D2= and D,,), which are produced by differential splicing (Dal Toso et al, 1989;Giros et al, 1989;Monsma et al, 1989). The activation of the receptor by interaction with dopamine or other antagonists results in various responses, including inhibition of adenylyl cyclase, inhibition of phosphatidylinositol turnover, increase in K' channel activity and inhibition of Ca2+ mobilization (Bigornia et al, 1988;Civelli et al, 1993;Creese et al, 1983;Lacey et al, 1987;Vallar and Meldolesi, 1989). The major problems that arise with the use of dopaminergic antipsychotic drugs are the side effects resulting from drug coupling to other neuroreceptors (Reynolds, 1992).…”

Catecholamine metabolic pathways and exercise training. Plasma and urine catecholamines, metabolic enzymes, and chromogranin-A.

“…During exercise training, prejunctional receptors could develop increased sensitivity to catecholamines to achieve catecholamine excretion similar to pretraining levels. Catecholamine release would then be "kept down" in a manner similar to the rapid suppression of adrenal medullary secretion by acute a2-adrenergic, /32-adrenergic, and dopaminergic receptor stimulation.54 56 This seems likely, because tyrosine hydroxylase activity, which is induced by stress (e.g., exercise training), is likely to be increased in well-trained individuals.…”