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Characterization of the adenosine receptors mediating hypothermia in the conscious mouse
Author(s) -
Anderson R.,
Sheehan M.J.,
Strong P.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17151.x
Subject(s) - cgs 21680 , adenosine , agonist , adenosine receptor , adenosine a1 receptor , medicine , endocrinology , chemistry , adenosine receptor antagonist , receptor , adenosine a3 receptor , pharmacology , biology
1 The effects of a range of adenosine receptor‐selective ligands on body temperature were investigated following intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injection in conscious mice. The compounds tested were the non‐selective adenosine receptor agonist 5′‐N‐ethyl‐carboxamidoadenosine (NECA), the adenosine A 1 receptor‐selective agonists cyclopentyl‐adenosine (CPA), N 6 ‐(9R‐phenyl‐isopropyl)‐adenosine (R‐PIA) and N‐(1S, trans )‐[2‐hydroxycyclopentyl]‐adenosine (GR79236), the A 2a receptor selective agonist 2‐[ p ‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS‐21680), the A 2b receptor agonist N‐[(2‐methylphenyl)methyl]adenosine (metrifudil) and the A 3 receptor agonist N 6 ‐(4‐aminophenylethyl)adenosine (APNEA). 2 NECA (0.01‐1 μg, i.c.v.), all of the A 1 ‐selective agonists (0.01‐1 μg, i.c.v.) and APNEA (0.1–3 μg i.c.v.) produced profound and dose‐related hypothermia and sedation. However, CGS‐21680 (0.1–10 μg i.c.v.) and metrifudil (0.01‐1 μg i.c.v.), produced only mild hypothermia at the highest doses tested. 3 The hypothermic response to the A 1 receptor‐selective agonists, GR79236 and R‐PIA was dose‐dependently antagonized by peripheral administration of either the non‐selective adenosine receptor antagonist, 8‐phenyltheophylline (8‐PT, approximately 40 and 30 fold rightward shifts of the dose‐response curves respectively at 10 mg kg −1 , i.p.), or the adenosine A 1 receptor‐selective antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, approximately 20 fold shift of the GR79236 dose‐response curve at 1 mg kg −1 , i.p.). The hypothermic response to APNEA was similarly dose‐dependently antagonized by the A 1 receptor‐selective antagonist, DPCPX (5 fold shift at 0.1 mg kg −1 , i.p.). 4 8( p ‐Sulphophenyl)theophylline (8‐SPT, 10 and 30 mg kg −1 , i.p.), a non‐selective adenosine receptor antagonist that penetrates the blood brain barrier poorly, produced only modest antagonism (approximately 2 fold shift at 30 mg kg −1 , i.p.) of the hypothermic response to GR79236. 5 These data suggest that hypothermia induced by adenosine analogues in the conscious mouse is mediated via adenosine Ai receptors, which are probably located in the CNS.