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Evidence that cyclic nucleotides are not mediators of fever in rabbits
Author(s) -
Dascombe M.J.
Publication year - 1984
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.1476-5381.1984.tb16122.x
Subject(s) - medicine , endocrinology , guanosine , adenosine , chemistry , cyclase , adenylate kinase , cyclic nucleotide , cholera toxin , adenosine monophosphate , hypothermia , nucleotide , hyperthermia , biology , biochemistry , enzyme , gene
1 The N 6 ‐2′‐0‐dibutyryl derivative of adenosine 3′,5′‐monophosphate (db cyclic AMP) and related compounds have been micro‐injected into the preoptic/anterior hypothalamic nuclei (PO/AH) of the unanaesthetized, restrained rabbit and the effects on deep body temperature observed. 2 Db cyclic AMP (100–400 μg) produced hypothermia of rapid onset in rabbits at an ambient temperature of 20–23 °C. Hypothermia was also produced by N 2 ‐2′‐0‐dibutyryl guanosine 3′,5′‐monophosphate (db cyclic GMP), but not by saline, sodium n ‐butyrate, adenosine 3′,5′‐monophosphate (cyclic AMP), guanosine 3′,5′‐monophosphate, adenosine 5′‐mono‐, di‐ or triphosphate. 3 The initial hypothermic response to db cyclic AMP and db cyclic GMP was followed by a sustained rise in temperature. However, all compounds injected into the PO/AH produced a similar hyperthermia which was attenuated by paracetamol. Development of this tissue‐damage fever abolished the hypothermic response to db cyclic AMP in some rabbits. 4 The effects of db cyclic AMP on body temperature and behaviour were not reproduced by the adenylate cyclase activators, cholera toxin (0.125‐5 μg) and guanyl imidodiphosphate (5–400 μg). 5 It is concluded that hypothermia is the principal effect of db cyclic AMP on body temperature when injected into the PO/AH in rabbits. These data do not support the proposal that endogenous cyclic AMP in the rabbit brain mediates pyrexia.