Coupling of the endothelin ETA and ETB receptors to Ca2+ mobilization and Ca2+ sensitization in vascular smooth muscle.
Effects of endothelins on cytosolic Ca2+ level ([Ca2+]i) and contraction were examined in the swine pulmonary artery and vein. In the artery, endothelin-1 and endothelin-3, but not sarafotoxin S6c and IRL 1620 (300 nM each), induced transient increase followed by sustained increase in [Ca2+]i and sustained contraction. These effects were inhibited by the ETA receptor antagonist, BQ-123. In the vein, endothelin-1 and endothelin-3 (300 nM each) induced sustained increase in [Ca2+]i and sustained contraction whereas sarafotoxin S6c and IRL 1620 (300 nM each) transiently increased both [Ca2+]i and contractile tension. The ETB receptor in the vein was desensitized by pretreatment with sarafotoxin S6c, abolishing the effects of sarafotoxin S6c and IRL 1620 without changing the effects of endothelin-1 and endothelin-3. In contrast, an ETB antagonist, RES-701-1, antagonized the effects of IRL 1620 without changing the effects of other stimulants. In both artery and vein, the maximum contraction induced by these stimulants was greater than that induced by KCl at a given [Ca2+]i. In the absence of external Ca2+, endothelin-1 and endothelin-3 induced transient increase in [Ca2+]i and slow sustained contraction in both artery and vein. In the vein, sarafotoxin S6c induced small sustained contraction without changing [Ca2+]i. In the permeabilized artery and vein, endothelin-1 augmented the contraction induced by Ca2+. These results suggest that the ETA receptors in the artery and vein are coupled to Ca2+ release (which does not seem to trigger contraction), Ca2+ influx and Ca2+ sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
Sudjarwo
S A
SA
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.
Hori
M
M
Tanaka
T
T
Matsuda
Y
Y
Karaki
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium