Premium
Evidence for ET A and ET B receptors in rat skin and an investigation of their function in the cutaneous microvasculature
Author(s) -
Lawrence E.,
Siney L.,
Wilsoncroft P.,
Knock G.A.,
Terenghi G.,
Polak J.M.,
Brain S.D.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15009.x
Subject(s) - vasoconstriction , endothelins , endocrinology , medicine , endothelin receptor , agonist , calcitonin gene related peptide , receptor , vasodilation , chemistry , antagonist , endothelin 1 , endothelin 3 , biology , neuropeptide
1 The relative contribution of ET A and ET B receptors in the response of rat skin to endothelins was investigated by use of the selective ET B agonist IRL‐1620 and the selective ET A antagonist BQ‐123. 2 Binding data suggest the presence of ET A and ET B receptors as preincubation with [Ala 3′11,18 Nle 7 ]‐endothelin‐1 reduced ET‐1 binding by approximately 40%. 3 Intradermal injection of endothelin‐1 (ET‐1, 1–10 pmol/site) and ET‐3 (3–100 pmol/site) induced a dose‐dependent decrease in local blood flow assessed by 133 Xe clearance at test sites in rat skin. 4 The endothelin analogue [Ala 3′11,18 Nle 7 ]‐ET‐l (30–1000 pmol/site) induced significant vasoconstriction ( P <0.05) at the highest doses used and the selective ET B receptor agonist, IRL‐1620 [Suc‐[Glu 9 , Ala 11,15 ] endothelin (8–21)], (0.01–100 pmol/site) acted in a potent manner to induce a significant ( P <0.01) dose‐dependent decrease in 133 Xe clearance. 5 Co‐injection with the selective ET A receptor antagonist, BQ‐123 (1 nmol/site), completely abolished the vasoconstriction to ET‐1 and partially to ET‐3, but had no effect on IRL‐1620‐induced vasoconstriction. In addition, IRL‐1620 responses were not altered at sites treated with submaximal doses of a nitric oxide synthase inhibitor or a prostaglandin synthase inhibitor. 6 ET‐1 and IRL‐1620 (100 fmol‐1 pmol/site) did not induce oedema formation as measured by [ 125 I]‐albumin accumulation in the presence or absence of the vasodilator, calcitonin gene‐related peptide (CGRP). ET‐1 (1–3 pmol/site) inhibited substance P‐induced oedema formation and this effect, suggested to be secondary to a vasoconstrictor effect, was significantly reversed by BQ‐123 (1 nmol/site). 7 The findings in this study indicate that there are ET A and ET B receptors in rat skin and agents which activate either receptor act to mediate a decrease in cutaneous blood flow, but have no effect on increased microvascular permeability.