Biomaterial Database

Adenosine receptor-mediated contraction and relaxation of guinea-pig isolated tracheal smooth muscle: effects of adenosine antagonists. 1988

S G Farmer, and B J Canning, and D E Wilkins

Nova Pharmaceutical Corporation, Baltimore, Maryland 21224.

1. The effects of several adenosine analogues and antagonists on guinea-pig isolated trachea have been examined. 2. 5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-methylcarboxamidoadenosine (MECA) and adenosine (in the presence and absence of dipyridamole) elicited concentration-dependent tracheal relaxation. 3. The R(-)- and S(+)-enantiomers of N6-(2-phenylisopropyl)adenosine (R-PIA and S-PIA respectively), N6-cyclohexyladenosine (CHA) and 2-chloroadenosine (CADO) caused contractions at low concentrations (0.05-2.0 microM), whereas at higher concentrations, relaxation resulted. 4. For tracheal relaxation, the adenosine analogues exhibited the following rank order of potency: NECA greater than CADO greater than R-PIA = MECA greater than S-PIA greater than adenosine. The rank order of potency for inducing contractions was R-PIA greater than CHA greater than CADO greater than S-PIA. These data suggest that relaxation is mediated by adenosine A2-receptors, whereas contraction is the result of activation of A1-receptors. 5. 8-Phenyltheophylline (8-PT), aminophylline, the triazoloquinazoline CGS 15943A and NPC205 (1,3-di-n-propyl-8-(4-hydroxyphenyl)xanthine) each inhibited the R-PIA-induced contractile response, whereas enprofylline was without effect. NPC205, aminophylline and 8-PT were competitive antagonists, but CGS15943A was non-competitive. 6. That the most potent antagonist was the A1-selective agent, NPC205 (pA2 = 7.80), further suggests that the contraction is mediated by A1-receptors. Moreover, NPC205 was 13 times more potent as an antagonist of R-PIA-induced contractions (A1) than of NECA-induced relaxations (A2). 7. The antagonists were also found to relax the trachea by an unknown mechanism. That enprofylline did not antagonize the R-PIA-induced contractions, but was 3-4 times more potent a tracheal relaxant than aminophylline, further suggests that a direct effect on airway smooth muscle, rather than antagonism of endogenous adenosine, is more relevant to the bronchodilator effect of alkylxanthines in the treatment of asthma.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009126	Muscle Relaxation	That phase of a muscle twitch during which a muscle returns to a resting position.	Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010660	Phenylisopropyladenosine	N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.	Isopropylphenyladenosine,L-Phenylisopropyladenosine,N(6)-Phenylisopropyl-Adenosine,L Phenylisopropyladenosine
D011983	Receptors, Purinergic	Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.	Methyladenine Receptors,Purine Receptors,Purinergic Receptor,Purinergic Receptors,Purinoceptors,Purine Receptor,Purinoceptor,Receptors, Methyladenine,Receptors, Purine,Receptor, Purine,Receptor, Purinergic
D004176	Dipyridamole	A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)	Antistenocardin,Apo-Dipyridamole,Cerebrovase,Cléridium,Curantil,Curantyl,Dipyramidole,Kurantil,Miosen,Novo-Dipiradol,Persantin,Persantine,Apo Dipyridamole,Novo Dipiradol
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000241	Adenosine	A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.	Adenocard,Adenoscan
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia