Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium

Worku Abebe, S. R. Makujina, S. J. Mustafa

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

This study was designed to investigate the effects of a series of adenosine analogues on porcine coronary artery in vitro. In both endothelium- intact and -denuded rings, 5'-(N-ethylcarboxamido)adenosine (NECA), 2-[p-(2- carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2- chloroadenosine (CAD), N6-R-phenylisopropyladenosine (R-PIA), 2- phenylaminoadenosine (PAA), N6-cyclohexyladenosine (CHA), N6- cyclopentyladenosine (CPA), and N6-S-phenylisopropyladenosine (S-PIA) produced concentration-dependent relaxations. The rank order of potency was consistent with A2-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl)theophylline (8-SPT), attenuated the relaxant responses to all the agonists in the endothelium-intact rings and to only CAD, R-PIA, PAA, CHA, CPA, and S-PIA in the denuded preparations. Except for NECA and CGS-21680, the slopes of the relaxation curves and the dissociation constant (K(b)) values for 8-SPT were similar for all agonists. In addition, endothelium removal selectively reduced the responses to NECA and CGS-21680. The adenosine receptor agonist, CGS-22988, also relaxed the denuded rings in a manner insensitive to blockade by 8-SPT. The data suggest that multiple A2-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery, mediating relaxation. Whereas the smooth muscle contains both xanthine-sensitive and -insensitive A2-receptors, which can be activated by a wide range of adenosine agonists, the endothelium possesses xanthine-sensitive receptors that can be stimulated selectively by certain adenosine agonists, including 5'-uronamide derivatives, such as NECA and CGS- 21680. The smooth muscle also appears to contain xanthine-insensitive A4- receptors activated by CGS-22988.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume266
Issue number5 35-5
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Purinergic P1 Receptors
Adenosine
Endothelium
Coronary Vessels
Swine
Phenylisopropyladenosine
Xanthine
Theophylline
Adenosine A2 Receptors
Smooth Muscle
2-Chloroadenosine
Adenosine-5'-(N-ethylcarboxamide)
Purinergic P1 Receptor Agonists
varespladib methyl
2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine

Keywords

  • 8-(sulfophenyl)theophylline
  • A-adenosine receptors
  • adenosine analogues
  • vascular smooth muscle
  • vasorelaxation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium. / Abebe, Worku; Makujina, S. R.; Mustafa, S. J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 266, No. 5 35-5, 01.01.1994.

Research output: Contribution to journalArticle

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AB - This study was designed to investigate the effects of a series of adenosine analogues on porcine coronary artery in vitro. In both endothelium- intact and -denuded rings, 5'-(N-ethylcarboxamido)adenosine (NECA), 2-[p-(2- carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2- chloroadenosine (CAD), N6-R-phenylisopropyladenosine (R-PIA), 2- phenylaminoadenosine (PAA), N6-cyclohexyladenosine (CHA), N6- cyclopentyladenosine (CPA), and N6-S-phenylisopropyladenosine (S-PIA) produced concentration-dependent relaxations. The rank order of potency was consistent with A2-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl)theophylline (8-SPT), attenuated the relaxant responses to all the agonists in the endothelium-intact rings and to only CAD, R-PIA, PAA, CHA, CPA, and S-PIA in the denuded preparations. Except for NECA and CGS-21680, the slopes of the relaxation curves and the dissociation constant (K(b)) values for 8-SPT were similar for all agonists. In addition, endothelium removal selectively reduced the responses to NECA and CGS-21680. The adenosine receptor agonist, CGS-22988, also relaxed the denuded rings in a manner insensitive to blockade by 8-SPT. The data suggest that multiple A2-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery, mediating relaxation. Whereas the smooth muscle contains both xanthine-sensitive and -insensitive A2-receptors, which can be activated by a wide range of adenosine agonists, the endothelium possesses xanthine-sensitive receptors that can be stimulated selectively by certain adenosine agonists, including 5'-uronamide derivatives, such as NECA and CGS- 21680. The smooth muscle also appears to contain xanthine-insensitive A4- receptors activated by CGS-22988.

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