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Effects of substance P on nicotine-induced intracellular Ca2+ dynamics in bovine adrenal chromaffin cells
1999
Suzuki, S. (Hokkaido Univ., Sapporo (Japan)) | Habara, Y. | Kanno, T.
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 (10-100mu-M) 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 10mu-M 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 a
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1993
Kang, T.M. | Cho, J.Y. | Yang, I.S. (Seoul National University, Seoul (Korea Republic). College of Veterinary Medicine) | Park, J.H. (Cheju National University, Cheju (Korea Republic). College of Agriculture)
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1991
Cho, J.Y. | Yang, I.S. (Seoul National Univ., Suwon (Korea Republic). Coll. of Veterinary Medicine)
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1994
Lim, H.J. | Han, H.J. | Han, G.K. (Chonnam National University, Kwangju (Korea Republic). College of Veterinary Medicine)