Japanese Journal of Veterinary Research;Volume 47, Number 1-2

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Effects of substance P on nicotine-induced intracellular Ca^<2+> dynamics in bovine adrenal chromaffin cells

SUZUKI, Syuka;HABARA, Yoshiaki;KANNNO, Tomio

Permalink : http://hdl.handle.net/2115/2724
JaLCDOI : 10.14943/jjvr.47.1-2.3
KEYWORDS : adrenal chromaffin cells;bovine;Ca^<2+>;fura-2;substance P

Abstract

Substance P (SP) is colocalized with ACh in splanchnic nerves that innervate into adrenal medulla and the peptide has been shown to inhibit nicotinic agonists-induced catecholamine secretion. To elucidate the effects of SP on cytosolic Ca^<2+> dynamics, the present study was conducted using fura-2-loaded isolated bovine adrenal chromaffin cells. Stimulation of the cells with nicotine (10-100μM) produced a rapid rise of cytosolic Ca^<2+> concentration ([Ca^<2+>]_i), the peak level of which increased in a dose-dependent manner, followed by a gradual decay. In the presence of 10μM SP, the dose-response relationship of the peak levels shifted downward. Quantitative analyses implied that SP inhibits the nicotine-induced Ca^<2+> influx in a noncompetitive manner. Nicotinic acetylcholine receptor is composed of two major functional domains : an agonist-binding site and an ionophore or channel domain. Agonist binding activates ionophore / channel domain and causes mainly Na^+ influx. This Na^+ influx depolarizes the cell and activates voltage-dependent Ca^<2+> channels. Based on this fact, the present results indicate that SP dose not block nicotine binding sites but interferes with other sites of nicotinic receptor / channel molecule, most probably a channel domain. It was suggested that SP colocalized with ACh in splanchnic nerves functions as a physiological modulator of catecholamine secretion by non-competitively suppressing ACh-induced cytosolic Ca^<2+> dynamics in bovine adrenal chromaffin cells.

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