Adenosine receptor-mediated relaxation of guinea-pig precontracted, isolated trachea.
1. We have investigated the pharmacological profile of the adenosine receptor mediating relaxation of the carbachol pre-contracted guinea-pig trachea. 2. 5'-N-Ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine elicited concentration-dependent relaxations with pD2 (-log10 half-maximal values) of 6.37 +/- 0.04 and 5.25 +/- 0.09, with maximal relaxations of 73 +/- 7 and 208 +/- 38%, respectively. In the presence of 10 microM NECA, 2-chloroadenosine was able to relax the tissue further with a pD2 value of 4.74 +/- 0.11 and a maximal response of 252 +/- 68%. 3. CGS 21680, APEC and adenosine failed to elicit significant relaxations of precontracted tracheal rings at concentrations below 10 microM. At 10 microM, adenosine analogues elicited relaxations with the following order of magnitude (% relaxation): 2-chloroadenosine (75 +/- 16%) = NECA (69 +/- 16%) > APEC (25 +/- 8%) > CGS 21680 (11 +/- 2%) > adenosine (6 +/- 4%). 4. NECA-induced relaxation of precontracted trachea was antagonized by adenosine receptor antagonists with the rank order of apparent affinity (Ki, nM): PD 115,199 (27 +/- 8) = XAC (43 +/- 11) > CP 66,713(285 +/- 89) = DPCPX (316 +/- 114). 5. We conclude that the adenosine analogue-induced relaxation of guinea-pig tracheal rings fails to fit into the current classification of A2 adenosine receptors.
Losinski
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A
Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
Alexander
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SP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014132:Trachea / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018721:Muscarinic Agonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D002217:Carbachol; D000241:Adenosine