Cellular mechanisms involved in rabbit carotid body excitation elicited by endothelin peptides.
The present study evaluated the effects of endothelin (ET) peptides on carotid sinus nerve (CSN) activity, catecholamine (CA) release, and second messenger signaling pathways in rabbit carotid bodies superfused in vitro, and in dissociated chemosensory type I cells. ET-1 (1.0 microM) and ET-3 (1.0 microM) did not alter basal CSN activity and CA release, but they potentiated nerve activity (P<0. 05) and CA release (P<0.05) evoked by hypoxia. Under basal conditions, ET-1 and ET-3 (1.0 microM each) elevated tissue cyclic AMP (cAMP) levels nearly 3-fold (P<0.001, ET-1; P<0.05, ET-3) and inositol phosphate (IP(n)) levels nearly 4-fold (P<0.01, ET-1). Hypoxia evoked an increase in carotid body cAMP, and this response was also potentiated in the presence of 1.0 microM ET-1 (P<0.01) or 1.0 microM ET-3 (P<0.001). Patch-clamp studies of isolated type I cells showed that 100 nM ET-1 elevated the peak amplitude of voltage-sensitive (L-type) Ca(2+)-currents by an average of 37.6% (P<0.001). Fluorescent Ca(2+)-imaging revealed that 100 nM ET-1 did not alter [Ca(2+)](i) under basal conditions, but that [Ca(2+)](i)-responses evoked by hypoxia were potentiated by 87% (P<0. 01). Our data indicate that ET augments chemoreceptor responses by activating second messenger signaling pathways which promote the phosphorylation of Ca(2+)-channel protein, thereby enhancing stimulus-evoked intracellular Ca(2+) levels.
Chen
J
J
Department of Physiology, University of Utah School of Medicine, 410 Chipeta Way, Research Park, Salt Lake City, UT 84108, USA.
He
L
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Dinger
B
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Fidone
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002344:Carotid Body / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D017466:Receptors, Endothelin / Q000819:agonists; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D015220:Calcium Channels; D002395:Catecholamines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007295:Inositol Phosphates; D017466:Receptors, Endothelin; D000242:Cyclic AMP; D002118:Calcium