Hypothermia-induced supersensitivity to adenosine for responses mediated via A1-receptors but not A2-receptors.
Four isolated tissues were examined in which the responses to adenosine are mediated via either A1- or A2-receptors. The responses examined were the inhibition of cholinergic transmission of field-stimulated guinea-pig ileum (A1), inhibition of noradrenergic transmission of field-stimulated rat vas deferens (A1), inhibition of developed tension of rat paced left atria (A1) and relaxation of carbachol-contracted guinea-pig trachea (A2). Cumulative concentration-response curves for adenosine and 2-chloroadenosine were constructed at 37, 30 or 27 degrees C. When plotted as a percentage of the maximum response, the concentration-response curves were displaced to the left by cooling in the ileum, vas deferens and atria, indicative of supersensitivity. This increase in sensitivity does not arise from inhibition of uptake or deamination by cooling, since it occurs equally for adenosine and 2-chloroadenosine, the latter being immune to these processes. In contrast, the sensitivity of the trachea was not affected (2-chloroadenosine) or reduced (adenosine) by cooling. Thus responses mediated via adenosine receptors of the A1 subtype exhibit hypothermia-induced supersensitivity, whereas those mediated via A2-receptors do not. This suggests a fundamental temperature-dependent difference between the two adenosine receptor subtypes.
Broadley
K J
KJ
Broome
S
S
Paton
D M
DM
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007035:Hypothermia / Q000503:physiopathology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011983:Receptors, Purinergic; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D002217:Carbachol; D000241:Adenosine