Interleukin-1 inhibits voltage-dependent P/Q-type Ca2+ channel associated with the inhibition of the rise of intracellular free Ca2+ concentration and catecholamine release in adrenal chromaffin cells
BBA_1673-3_160-169_2004-8-4.pdf 1.16 MB
Voltage-dependent Ca2+ channel
P/Q-type Ca2+ channel
Adrenal chromaffin cells
Effects of interleukin (IL) on intracellular free Ca2+ concentration ([Ca2+]i) rise and catecholamine (CA) release were examined in isolated, cultured bovine adrenal chromaffin cells. IL-1α and IL-1β inhibited the rise of [Ca2+]i and CA release induced by acetylcholine (ACh) and excess KCl both in normal and in Ca2+-sucrose medium. IL-1 receptor antagonist, IL-1RA by pretreatment blocked the inhibitory actions of IL-1. IL-1α reduced CA release induced by veratridine in normal medium but not in the presence of diltiazem. Analysis using specific blockers for voltage-operated Ca2+ channels revealed that IL-1α specifically inhibited the P/Q-type Ca2+ channel to reduce [Ca2+]i rise induced by excess KCl. IL-1 did not affect [Ca2+]i rise induced either by bradykinin or caffeine in Ca2+- deprivated medium or via activation of store-operated Ca2+ channel. The inhibitory effects of IL-1 were blocked by pretreatments of cells with herbimycin A, U0126 and PD 98054, but not with SB202190, SP 600125 or pertussis toxin (PTX), inhibited the induction of the inhibitory action of IL-1.These results demonstrated that IL-1 inhibits stimulation-evoked [Ca2+]i rise and CA release in chromaffin cells by blocking voltage-operated P/O-type Ca2+ channels. The inhibitory action of IL-1 may be mediated through tyrosine kinase and MEK/ERK pathways.
Biochimica et Biophysica Acta
Copyright (c) 2004 Elsevier B.V