Effects of adenosine and two stable adenosine analogues on blood pressure, heart rate and colonic temperature in the rat.
Adenosine exerts effects via receptors of the AI- and A2-subtype. L-phenylisopropyl adenosine (L-PIA) is more potent than N-5'-ethylcarboxamido adenosine (NECA) at the A1-subtype receptor whereas the potency order is reversed at the A2-subtype receptor. Adenosine analogues have been shown to decrease blood pressure and heart rate and to induce a marked hypothermia. In the present series of experiments adenosine, L-PIA and NECA were given i.p. or i.v. to rats, and blood pressure, ECG and colonic temperature were recorded. The NECA was the most potent of the compounds in reducing blood pressure (EC50 2 micrograms kg-1 i.v.), followed by L-PIA (EC50 approximately 30 micrograms kg-1 i.v.) and adenosine (EC50 approximately 300 micrograms kg-1 i.v.). In contrast, L-PIA and NECA were equally active in reducing heart rate (EC50 approximately 6 micrograms kg-1 i.v.). and considerably more potent than adenosine (EC50 approximately 300 micrograms kg-1 i.v.). It is suggested that simultaneous measurement of blood pressure and heart rate could be a simple in vivo model for comparison of A1- and A2-receptor subtype mediated effects. Colonic temperature was markedly reduced after i.p. administration of the adenosine analogues. Thus, 100 micrograms NECA kg-1 reduced colonic temperature from 37.8 to 26 degrees C. A 5 degrees C temperature drop was obtained by 10 micrograms kg-1 NECA, by 200 micrograms kg-1 L-PIA and by 200 mg kg-1 adenosine. The fall in colonic temperature was associated with a loss of muscular activity, as determined by needle electrodes or by palpation, indicating an inhibition of shivering.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D003106:Colon / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D014665:Vasodilator Agents / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine