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Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin.
Am J Physiol. 1998 10; 275(4):R1066-74.AJ

Abstract

We investigated the functional importance and signal transduction pathways of endothelin (ET)-B receptors in mediating ET-1-induced vasoconstriction in pig skin. Skin vasoconstriction was studied by monitoring the perfusion pressure of isolated perfused pig skin flaps (6 x 16 cm) at a constant flow rate. Intra-arterial infusion of the ETA/B receptor agonist ET-1, the ETB receptor agonists sarafotoxin 6C (S6c) and BQ-3020, or the thromboxane A2 mimetic U-46619 (n = 4 or 5) caused a concentration-dependent skin vasoconstriction. The vasoconstrictor potency of ET-1 (EC50 3.1 x 10(-9) M) was lower (P < 0.05) than that of S6c (EC50 1.8 x 10(-9) M) and similar to that of BQ-3020 (EC50 2.6 x 10(-9) M). The vasoconstrictor potency of ET-1, S6c, and BQ-3020 was at least 300-fold higher than that of U-46619 (EC50 0.9 x 10(-6) M). The skin vasoconstrictor effect of ET-1 (10(-9)-10(-8) M) was partially inhibited by 10(-5) M BQ-123, an ETA receptor antagonist. Further inhibition was achieved with the combination of 10(-5) M BQ-123 and BQ-788 (an ETB receptor antagonist) or with an ETA/B receptor antagonist (10(-5) M bosentan or PD-145065) (n = 5; P < 0.05). In addition, the skin vasoconstrictor effect of the ETB receptor agonist BQ-3020 was completely blocked by 5 x 10(-6) M BQ-788 and partially inhibited by 5 x 10(-6) M of the phospholipase C (PLC) inhibitor 2-nitro-4-carboxyl-N,N-diphenylcarbamate (NCDC), an L-type Ca2+ channel antagonist (nifedipine), a protein kinase C (PKC) inhibitor (chelerythrine), or removal of Ca2+ from the perfusate (n = 4 or 5; P < 0.05). The vasoconstrictor effect of S6c was also partially blocked by 5 x 10(-6) M of NCDC, nifedipine, or chelerythrine or by removal of Ca2+ from the perfusate (n = 4; P < 0. 01). We conclude that ETB receptors play a central role in mediating ET-1-induced vasoconstriction in pig skin, and the mechanism probably involves L-type Ca2+ channels, PLC, and PKC.

Authors+Show Affiliations

The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X8.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9756535

Citation

Pang, C Y., et al. "Role and Mechanism of endothelin-B Receptors in Mediating ET-1-induced Vasoconstriction in Pig Skin." The American Journal of Physiology, vol. 275, no. 4, 1998, pp. R1066-74.
Pang CY, Zhang J, Xu H, et al. Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin. Am J Physiol. 1998;275(4):R1066-74.
Pang, C. Y., Zhang, J., Xu, H., Lipa, J. E., Forrest, C. R., & Neligan, P. C. (1998). Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin. The American Journal of Physiology, 275(4), R1066-74. https://doi.org/10.1152/ajpregu.1998.275.4.R1066
Pang CY, et al. Role and Mechanism of endothelin-B Receptors in Mediating ET-1-induced Vasoconstriction in Pig Skin. Am J Physiol. 1998;275(4):R1066-74. PubMed PMID: 9756535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role and mechanism of endothelin-B receptors in mediating ET-1-induced vasoconstriction in pig skin. AU - Pang,C Y, AU - Zhang,J, AU - Xu,H, AU - Lipa,J E, AU - Forrest,C R, AU - Neligan,P C, PY - 1998/10/2/pubmed PY - 1998/10/2/medline PY - 1998/10/2/entrez SP - R1066 EP - 74 JF - The American journal of physiology JO - Am J Physiol VL - 275 IS - 4 N2 - We investigated the functional importance and signal transduction pathways of endothelin (ET)-B receptors in mediating ET-1-induced vasoconstriction in pig skin. Skin vasoconstriction was studied by monitoring the perfusion pressure of isolated perfused pig skin flaps (6 x 16 cm) at a constant flow rate. Intra-arterial infusion of the ETA/B receptor agonist ET-1, the ETB receptor agonists sarafotoxin 6C (S6c) and BQ-3020, or the thromboxane A2 mimetic U-46619 (n = 4 or 5) caused a concentration-dependent skin vasoconstriction. The vasoconstrictor potency of ET-1 (EC50 3.1 x 10(-9) M) was lower (P < 0.05) than that of S6c (EC50 1.8 x 10(-9) M) and similar to that of BQ-3020 (EC50 2.6 x 10(-9) M). The vasoconstrictor potency of ET-1, S6c, and BQ-3020 was at least 300-fold higher than that of U-46619 (EC50 0.9 x 10(-6) M). The skin vasoconstrictor effect of ET-1 (10(-9)-10(-8) M) was partially inhibited by 10(-5) M BQ-123, an ETA receptor antagonist. Further inhibition was achieved with the combination of 10(-5) M BQ-123 and BQ-788 (an ETB receptor antagonist) or with an ETA/B receptor antagonist (10(-5) M bosentan or PD-145065) (n = 5; P < 0.05). In addition, the skin vasoconstrictor effect of the ETB receptor agonist BQ-3020 was completely blocked by 5 x 10(-6) M BQ-788 and partially inhibited by 5 x 10(-6) M of the phospholipase C (PLC) inhibitor 2-nitro-4-carboxyl-N,N-diphenylcarbamate (NCDC), an L-type Ca2+ channel antagonist (nifedipine), a protein kinase C (PKC) inhibitor (chelerythrine), or removal of Ca2+ from the perfusate (n = 4 or 5; P < 0.05). The vasoconstrictor effect of S6c was also partially blocked by 5 x 10(-6) M of NCDC, nifedipine, or chelerythrine or by removal of Ca2+ from the perfusate (n = 4; P < 0. 01). We conclude that ETB receptors play a central role in mediating ET-1-induced vasoconstriction in pig skin, and the mechanism probably involves L-type Ca2+ channels, PLC, and PKC. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/9756535/Role_and_mechanism_of_endothelin_B_receptors_in_mediating_ET_1_induced_vasoconstriction_in_pig_skin_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.1998.275.4.R1066?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -