Effects of Substance P on Carbachol‐Stimulated 45Ca2+ Uptake into Cultured Adrenal Chromaffin Cells

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Abstract
Substance P is known to modulate acetylcholine‐induced catecholamine release from adrenal chromaffin cells. To investigate the mechanisms involved in this modulation, the present study examined the effects of substance P on net 45Ca2+ fluxes in cultures of bovine adrenal chromaffin cells. Two effects of substance P were observed: (1) Substance P inhibited carbachol‐induced 45Ca2+ uptake and 45Ca2+ efflux and (2) substance P protected against desensitization of carbachol‐induced 45Ca2+ uptake and 45Ca2+ efflux. Thus substance P modulates two other cholinergic responses, 45Ca2+ uptake and 45Ca2+ efflux, in a manner similar to its modulation of catecholamine release. The results also indicate that substance P's inhibition of net carbachol‐induced 45Ca2+ uptake is due to inhibition of 45Ca2+ uptake rather than enhancement of 45Ca2+ efflux. Substance P almost completely inhibited carbachol‐induced 45Ca2+ uptake in both Na+‐containing and Na+‐free media, suggesting that substance P can inhibit the uptake of 45Ca2+ induced by carbachol regardless of whether 45Ca2+ is taken up through voltage‐sensitive or acetylcholine receptor‐linked channels. However, substance P produced only a small inhibition of K+‐induced 45Ca2+ uptake, indicating that substance P does not interact directly with voltage‐sensitive Ca2+ channels. In addition, substance P's inhibition of carbachol‐induced 45Ca2+ uptake was noncompetitive with respect to Ca2+, and increasing concentrations of extracellular Ca2+ were unable to overcome substance P's inhibition of [3H]‐norepinephrine ([3H]NE) release. It is concluded that substance P does not interact directly with Ca2+ channels in bovine adrenal chromaffin cells.