TY - JOUR
T1 - A2‐purinoceptor‐mediated relaxation in the guinea‐pig coronary vasculature
T2 - a role for nitric oxide
AU - Vials, Amanda
AU - Burnstock, Geoffrey
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1993/6
Y1 - 1993/6
N2 - The Langendorff heart preparation was used to investigate the mechanism of action of the endothelium‐dependent vasodilatation evoked by adenosine and its analogues in the guinea‐pig coronary vasculature. The relative order of potency of adenosine and its analogues in causing a reduction in perfusion pressure was d‐5′‐(N‐ethylcarboxamide)adenosine (NECA) = 2‐[p‐(2‐carboxyethyl)phenylethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680)>R‐N6‐(2‐phenylisopropyl)adenosine (R‐PIA) = adenosine = 2‐chloroadenosine (2‐CA)>S‐N6‐(2‐phenylisopropyl)adenosine (S‐PIA) = N6‐cyclopentyl‐adenosine (CPA); thus suggesting the presence of A2‐purinoceptors in this preparation. 8‐(p‐Sulphophenyl)theophylline (8‐PSPT; 3 × 10−5 m) significantly reduced both the maximum amplitude and area of the vasodilatation produced in response to adenosine (5 × 10−10 − 5 × 10−8 mol) without having any effect on the response to the P2‐purinoceptor agonist, 2‐methylthioATP. The relaxation induced by adenosine (5 × 10−12 − 5 × 10−8 mol) was unaffected by the selective A1‐purinoceptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX; 10−8 m). This antagonist profile suggests that only A2‐purinoceptors are present in the guinea‐pig coronary vasculature. The areas of the vasodilator response to adenosine (5 × 10−10 − 5 × 10−7 mol), NECA (5 × 10−12 − 5 × 10−7 mol) and CGS 21680 (5 × 10−12 − 5 × 10−10 mol) were significantly reduced by NG‐nitro‐l‐arginine methyl ester (l‐NAME; 3 × 10−5 m). The amplitude of the responses to low concentrations of adenosine (5 × 10−10 − 5 × 10−9 mol), NECA (5 × 10−11 mol) and CGS 21680 (5 × 10−11 − 5 × 10−9 mol) were significantly reduced by l‐NAME (3 × 10−5 m). l‐Arginine (1.5 × 10−3m) significantly reversed the inhibition, by l‐NAME (3 × 10−5m), of the relaxant response to adenosine (5 × 10−8 mol), NECA (5 × 10−9 mol) and CGS 21680 (5 × 10−11 mol). Indomethacin (10−6 m) did not inhibit the response to adenosine, except at low doses (5 × 10−11 − 5 × 10−10 mol). It is concluded that in the guinea‐pig coronary vasculature, while a major part of the vasodilator action of adenosine is probably directly via A2‐receptors on the smooth muscle, activation of a subpopulation of A2‐purinoceptors on endothelial cells by adenosine and its analogues induces relaxation via production of nitric oxide; prostanoids appear to play a minimal role in the relaxation induced by adenosine as in most other preparations. 1993 British Pharmacological Society
AB - The Langendorff heart preparation was used to investigate the mechanism of action of the endothelium‐dependent vasodilatation evoked by adenosine and its analogues in the guinea‐pig coronary vasculature. The relative order of potency of adenosine and its analogues in causing a reduction in perfusion pressure was d‐5′‐(N‐ethylcarboxamide)adenosine (NECA) = 2‐[p‐(2‐carboxyethyl)phenylethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680)>R‐N6‐(2‐phenylisopropyl)adenosine (R‐PIA) = adenosine = 2‐chloroadenosine (2‐CA)>S‐N6‐(2‐phenylisopropyl)adenosine (S‐PIA) = N6‐cyclopentyl‐adenosine (CPA); thus suggesting the presence of A2‐purinoceptors in this preparation. 8‐(p‐Sulphophenyl)theophylline (8‐PSPT; 3 × 10−5 m) significantly reduced both the maximum amplitude and area of the vasodilatation produced in response to adenosine (5 × 10−10 − 5 × 10−8 mol) without having any effect on the response to the P2‐purinoceptor agonist, 2‐methylthioATP. The relaxation induced by adenosine (5 × 10−12 − 5 × 10−8 mol) was unaffected by the selective A1‐purinoceptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX; 10−8 m). This antagonist profile suggests that only A2‐purinoceptors are present in the guinea‐pig coronary vasculature. The areas of the vasodilator response to adenosine (5 × 10−10 − 5 × 10−7 mol), NECA (5 × 10−12 − 5 × 10−7 mol) and CGS 21680 (5 × 10−12 − 5 × 10−10 mol) were significantly reduced by NG‐nitro‐l‐arginine methyl ester (l‐NAME; 3 × 10−5 m). The amplitude of the responses to low concentrations of adenosine (5 × 10−10 − 5 × 10−9 mol), NECA (5 × 10−11 mol) and CGS 21680 (5 × 10−11 − 5 × 10−9 mol) were significantly reduced by l‐NAME (3 × 10−5 m). l‐Arginine (1.5 × 10−3m) significantly reversed the inhibition, by l‐NAME (3 × 10−5m), of the relaxant response to adenosine (5 × 10−8 mol), NECA (5 × 10−9 mol) and CGS 21680 (5 × 10−11 mol). Indomethacin (10−6 m) did not inhibit the response to adenosine, except at low doses (5 × 10−11 − 5 × 10−10 mol). It is concluded that in the guinea‐pig coronary vasculature, while a major part of the vasodilator action of adenosine is probably directly via A2‐receptors on the smooth muscle, activation of a subpopulation of A2‐purinoceptors on endothelial cells by adenosine and its analogues induces relaxation via production of nitric oxide; prostanoids appear to play a minimal role in the relaxation induced by adenosine as in most other preparations. 1993 British Pharmacological Society
KW - A‐purinoceptors
KW - Nitric oxide
KW - adenosine
KW - coronary vasculature
KW - endothelium
UR - http://www.scopus.com/inward/record.url?scp=0027336631&partnerID=8YFLogxK
U2 - 10.1111/j.1476-5381.1993.tb13586.x
DO - 10.1111/j.1476-5381.1993.tb13586.x
M3 - Article
C2 - 8358543
AN - SCOPUS:0027336631
SN - 0007-1188
VL - 109
SP - 424
EP - 429
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 2
ER -