Biomaterial Database

Adenosine A1 and A2 receptor agonists alter cardiac functions and prostacyclin release in the isolated guinea-pig heart. 1994

A Felsch, and K Stöcker, and U Borchard

Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.

The actions of the adenosine A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine) and the adenosine A2 receptor agonist CGS 21680 (2-[p-(2-carboxyethyl(phenethylamino]-5'-N- ethylcarboxamidoadenosine) on myocardial functions and prostacyclin release were studied in Langendorff-perfused guinea-pig hearts. In spontaneously beating hearts, perfused at constant pressure, CCPA reduced heart rate and left ventricular actively developed pressure with EC50 values of 54.4 +/- 8.7 nM and 81 +/- 6.2 nM, respectively. The adenosine A1 receptor antagonist PACPX (1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine, 1 microM) antagonized the effects of CCPA on heart rate and left ventricular actively developed pressure and increased the EC50 values 11-fold and 8-fold, respectively. CGS 21680 caused vasodilatation and doubled the coronary flow rate (EC50 of 5.77 +/- 3 nM). The potent but non-selective adenosine receptor antagonist CGS 15943A (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin++ +-5-imine, 0.1 microM) caused a shift to the right of the concentration-response curve of CGS 21680 for coronary flow rate and increased the EC50 value 52-fold. In electrically paced hearts, perfused at constant flow rate, CCPA (1-100 nM) and CGS 21680 (10-1000 nM) increased the 6-oxo-prostaglandin F1 alpha release (stable non-enzymatic hydrolysis product of prostacyclin) into the cardiac effluent to a maximum of 170 +/- 16% and 184 +/- 6%, respectively. The effects of CCPA and CGS 21680 on cardiac functions indicate a high selectivity of both agonists for adenosine A1 and A2 receptor subtypes of the isolated guinea-pig heart, respectively. The elevation of 6-oxo-prostaglandin F1 alpha in the effluent of guinea-pig hearts by CCPA and CGS 21680 is possibly independent of stimulation of adenosine receptors on the vascular endothelium.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010627	Phenethylamines	A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)	Phenylethylamines
D011464	Epoprostenol	A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).	Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D011799	Quinazolines	A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.	Quinazoline
D002304	Cardiac Pacing, Artificial	Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.	Pacing, Cardiac, Artificial,Artificial Cardiac Pacing,Artificial Cardiac Pacings,Cardiac Pacings, Artificial,Pacing, Artificial Cardiac,Pacings, Artificial Cardiac
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003326	Coronary Circulation	The circulation of blood through the CORONARY VESSELS of the HEART.	Circulation, Coronary
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums