Cellular mechanisms involved in rabbit carotid body excitation elicited byendothelin peptides

The present study evaluated the effects of endothelin (ET) peptides on caro tid sinus nerve (CSN) activity, catecholamine (CA) release, and second mess enger signaling pathways in rabbit carotid bodies superfused in vitro, and in dissociated chemosensory type I cells. ET-1 (1.0 mu M) and ET-3 (1.0 mu M) did not alter basal CSN activity and CA release, but they potentiated ne rve activity (P < 0.05) and CA release (P < 0.05) evoked by hypoxia. Under basal conditions, ET-1 and ET-3 (1.0 mu M each) elevated tissue cyclic AMP (cAMP) levels nearly 3-fold (P < 0.001, ET-1; P < 0.05, ET-3) and inositol phosphate (IPn) levels nearly 4-fold (P < 0.01, ET-1). Hypoxia evoked an in crease in carotid body cAMP, and this response was also potentiated in the presence of 1.0 mu M ET-1 (P < 0.01) or 1.0 mu M ET-3 (P < 0.001). Patch-cl amp studies of isolated type I cells showed that 100 nM ET-1 elevated the p eak amplitude of voltage-sensitive (L-type) Ca2+-currents by an average of 37.6% (P < 0.001). Fluorescent Ca2+-imaging revealed that 100 nM ET-1 did n ot alter [Ca2+](i) under basal conditions, but that [Ca2+](i)-responses evo ked by hypoxia were potentiated by 87% (P < 0.01). Our data indicate that E T augments chemoreceptor responses by activating second messenger signaling pathways which promote the phosphorylation of Ca2+-channel protein, thereb y enhancing stimulus-evoked intracellular Ca2+ levels. (C) 2000 Elsevier Sc ience B.V. All rights reserved.