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Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems.
Br J Pharmacol. 1993 Sep; 110(1):435-41.BJ

Abstract

1. Quantitative autoradiographic, biochemical and functional studies were performed to investigate the endothelin receptor subtypes and signal transduction systems that mediate endothelin-1 (ET-1)-induced contraction in rat isolated tracheal smooth muscle. 2. Specific binding of 0.5 nM [125I]-ET-1 to tracheal smooth muscle was inhibited by at least 40% in the presence of either the ETA receptor selective ligand BQ-123 (1 microM) or the ETB receptor-selective ligand sarafotoxin S6c (30 nM), indicating the presence of both ETA and ETB receptors in this tissue. 3. ET-1 and sarafotoxin S6c were both potent spasmogens of rat isolated tracheal smooth muscle preparations. Sarafotoxin S6c-induced contractions were unaffected in the presence of the ETA receptor antagonist BQ-123 (10 microM), but were markedly attenuated in tissue previously exposed to 100 nM sarafotoxin S6c to induce ETB receptor desensitization. ET-1-induced contractions were, at most, only partially attenuated either by blocking the ETA receptor-effector system (with 10 microM BQ-123) or by desensitizing the ETB receptor-effector system with sarafotoxin S6c. However, ET-1-induced contractions were markedly attenuated by blocking both receptor-effector systems simultaneously. These findings suggest that ET-1 could induce contraction by stimulating either ETA or ETB receptors. 4. ET-1 (10 microM) induced a 7 fold increase in intracellular [3H]-inositol phosphate accumulation over basal levels in rat isolated tracheal smooth muscle. In contrast, sarafotoxin S6c (2.5 microM) increased intracellular [3H]-inositol phosphate accumulation by only 2 fold. ET-1-induced accumulation of [3H]-inositol phosphates was abolished by 10 microM BQ-123. 5. In Ca2+-free Krebs bicarbonate solution, 100 nM ET-1 induced a significantly larger contraction than that induced by 100 nM sarafotoxin S6c (46.6 +/- 5.6% C,., versus 8.8 +/- 2.8% Cmax, n = 5-7). This presumed intracellular Ca2+-dependent phase of contraction induced by ET-1 was significantly inhibited by 10 microM BQ-123 (7.5 +/- 1.0% C.). Subsequent addition of 2.5 mM Ca2+ induced a second phase of contraction. The extracellular Ca2+-dependent phase of contraction induced by ET-1 was similar inmagnitude to that induced by sarafotoxin S6c (63.6 +/- 4.5% C.. versus 58.0 +/- 3.7% C.) and was not inhibited by BQ-123. Sarafotoxin S6c-induced contractions were not inhibited by the L-type Ca2+-channel antagonists, nicardipine or verapamil.6. In summary, ETA and ETB receptors coexist in rat isolated tracheal smooth muscle and stimulation of both receptor subtypes contributes to ET-l-induced contraction in this tissue. However, stimulation of these receptor subtypes appears to induce contraction by activating different second messenger pathways; ETA receptor stimulation induces phosphoinositide turnover and subsequent release of intracellular Ca2+ whereas stimulation of ETB receptors facilitates the influx of extracellular Ca2+.

Authors+Show Affiliations

Department of Pharmacology, University of Western Australia, Nedlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8220905

Citation

Henry, P J.. "Endothelin-1 (ET-1)-induced Contraction in Rat Isolated Trachea: Involvement of ETA and ETB Receptors and Multiple Signal Transduction Systems." British Journal of Pharmacology, vol. 110, no. 1, 1993, pp. 435-41.
Henry PJ. Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems. Br J Pharmacol. 1993;110(1):435-41.
Henry, P. J. (1993). Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems. British Journal of Pharmacology, 110(1), 435-41.
Henry PJ. Endothelin-1 (ET-1)-induced Contraction in Rat Isolated Trachea: Involvement of ETA and ETB Receptors and Multiple Signal Transduction Systems. Br J Pharmacol. 1993;110(1):435-41. PubMed PMID: 8220905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems. A1 - Henry,P J, PY - 1993/9/1/pubmed PY - 1993/9/1/medline PY - 1993/9/1/entrez SP - 435 EP - 41 JF - British journal of pharmacology JO - Br J Pharmacol VL - 110 IS - 1 N2 - 1. Quantitative autoradiographic, biochemical and functional studies were performed to investigate the endothelin receptor subtypes and signal transduction systems that mediate endothelin-1 (ET-1)-induced contraction in rat isolated tracheal smooth muscle. 2. Specific binding of 0.5 nM [125I]-ET-1 to tracheal smooth muscle was inhibited by at least 40% in the presence of either the ETA receptor selective ligand BQ-123 (1 microM) or the ETB receptor-selective ligand sarafotoxin S6c (30 nM), indicating the presence of both ETA and ETB receptors in this tissue. 3. ET-1 and sarafotoxin S6c were both potent spasmogens of rat isolated tracheal smooth muscle preparations. Sarafotoxin S6c-induced contractions were unaffected in the presence of the ETA receptor antagonist BQ-123 (10 microM), but were markedly attenuated in tissue previously exposed to 100 nM sarafotoxin S6c to induce ETB receptor desensitization. ET-1-induced contractions were, at most, only partially attenuated either by blocking the ETA receptor-effector system (with 10 microM BQ-123) or by desensitizing the ETB receptor-effector system with sarafotoxin S6c. However, ET-1-induced contractions were markedly attenuated by blocking both receptor-effector systems simultaneously. These findings suggest that ET-1 could induce contraction by stimulating either ETA or ETB receptors. 4. ET-1 (10 microM) induced a 7 fold increase in intracellular [3H]-inositol phosphate accumulation over basal levels in rat isolated tracheal smooth muscle. In contrast, sarafotoxin S6c (2.5 microM) increased intracellular [3H]-inositol phosphate accumulation by only 2 fold. ET-1-induced accumulation of [3H]-inositol phosphates was abolished by 10 microM BQ-123. 5. In Ca2+-free Krebs bicarbonate solution, 100 nM ET-1 induced a significantly larger contraction than that induced by 100 nM sarafotoxin S6c (46.6 +/- 5.6% C,., versus 8.8 +/- 2.8% Cmax, n = 5-7). This presumed intracellular Ca2+-dependent phase of contraction induced by ET-1 was significantly inhibited by 10 microM BQ-123 (7.5 +/- 1.0% C.). Subsequent addition of 2.5 mM Ca2+ induced a second phase of contraction. The extracellular Ca2+-dependent phase of contraction induced by ET-1 was similar inmagnitude to that induced by sarafotoxin S6c (63.6 +/- 4.5% C.. versus 58.0 +/- 3.7% C.) and was not inhibited by BQ-123. Sarafotoxin S6c-induced contractions were not inhibited by the L-type Ca2+-channel antagonists, nicardipine or verapamil.6. In summary, ETA and ETB receptors coexist in rat isolated tracheal smooth muscle and stimulation of both receptor subtypes contributes to ET-l-induced contraction in this tissue. However, stimulation of these receptor subtypes appears to induce contraction by activating different second messenger pathways; ETA receptor stimulation induces phosphoinositide turnover and subsequent release of intracellular Ca2+ whereas stimulation of ETB receptors facilitates the influx of extracellular Ca2+. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/8220905/Endothelin_1__ET_1__induced_contraction_in_rat_isolated_trachea:_involvement_of_ETA_and_ETB_receptors_and_multiple_signal_transduction_systems_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1188&date=1993&volume=110&issue=1&spage=435 DB - PRIME DP - Unbound Medicine ER -