Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1975 Aug;250(1):143–160. doi: 10.1113/jphysiol.1975.sp011046

The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature.

M J Dascombe, A S Milton
PMCID: PMC1348342  PMID: 170396

Abstract

1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins.

Full text

PDF
143

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bligh J., Milton A. S. The thermoregulatory effects of prostaglandin E 1 when infused into a lateral cerebral ventricle of the Welsh Mountain sheep at different ambient temperatures. J Physiol. 1973 Feb;229(1):30P–31P. [PubMed] [Google Scholar]
  2. Bowman W. C., Hall M. T. Inhibition of rabbit intestine mediated by alpha- and beta-adrenoceptors. Br J Pharmacol. 1970 Feb;38(2):399–415. doi: 10.1111/j.1476-5381.1970.tb08528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breckenridge B. M., Lisk R. D. Cyclic adenylate and hypothalamic regulatory functions. Proc Soc Exp Biol Med. 1969 Jul;131(3):934–935. doi: 10.3181/00379727-131-34012. [DOI] [PubMed] [Google Scholar]
  4. Chambaut A. M., Eboué-Bonis D., Hanoune J., Clauser H. Antagonistic actions between dibutyryl adenosine-3',5'-cyclic monophosphate and insulin on the metabolism of the surviving rat diaphragm. Biochem Biophys Res Commun. 1969 Feb 7;34(3):283–290. doi: 10.1016/0006-291x(69)90829-8. [DOI] [PubMed] [Google Scholar]
  5. Clark W. G., Cumby H. R., Davis N. E., 4th The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat. J Physiol. 1974 Jul;240(2):493–504. doi: 10.1113/jphysiol.1974.sp010619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper K. E., Cranston W. I., Honour A. J. Effects of intraventricular and intrahypothalamic injection of noradrenaline and 5-HT on body temperature in conscious rabbits. J Physiol. 1965 Dec;181(4):852–864. doi: 10.1113/jphysiol.1965.sp007801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dey P. K., Feldberg W., Gupta K. P., Milton A. S., Wendlandt S. Further studies on the role of prostaglandin in fever. J Physiol. 1974 Sep;241(3):629–646. doi: 10.1113/jphysiol.1974.sp010675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FELDBERG W., MYERS R. D. CHANGES IN TEMPERATURE PRODUCED BY MICRO-INJECTIONS OF AMINES INTO THE ANTERIOR HYPOTHALAMUS OF CATS. J Physiol. 1965 Mar;177:239–245. doi: 10.1113/jphysiol.1965.sp007589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FELDBERG W., MYERS R. D. EFFECTS ON TEMPERATURE OF AMINES INJECTED INTO THE CEREBRAL VENTRICLES. A NEW CONCEPT OF TEMPERATURE REGULATION. J Physiol. 1964 Sep;173:226–231. doi: 10.1113/jphysiol.1964.sp007454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feldberg W., Gupta K. P., Milton A. S., Wendlandt S. Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. J Physiol. 1973 Oct;234(2):279–303. doi: 10.1113/jphysiol.1973.sp010346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feldberg W., Gupta K. P. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol. 1973 Jan;228(1):41–53. doi: 10.1113/jphysiol.1973.sp010071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feldberg W., Myers R. D., Veale W. L. Perfusion from cerebral ventricle to cisterna magna in the unanaesthetized cat. Effect of calcium on body temperature. J Physiol. 1970 Apr;207(2):403–416. doi: 10.1113/jphysiol.1970.sp009069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feldberg W., Saxena P. N. Fever produced by prostaglandin E1. J Physiol. 1971 Sep;217(3):547–556. doi: 10.1113/jphysiol.1971.sp009585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Feldberg W., Saxena P. N. Mechanism of action of pyrogen. J Physiol. 1970 Nov;211(1):245–261. doi: 10.1113/jphysiol.1970.sp009277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Flower R. J., Vane J. R. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972 Dec 15;240(5381):410–411. doi: 10.1038/240410a0. [DOI] [PubMed] [Google Scholar]
  16. Gessa G. L., Krishna G., Forn J., Tagliamonte A., Brodie B. B. Behavioral and vegetative effects produced by dibutyryl cyclic AMP injected into different areas of the brain. Adv Biochem Psychopharmacol. 1970;3:371–381. [PubMed] [Google Scholar]
  17. Hadley M. E., Goldman J. M. Effects of cyclic 3',5'-AMP and other adenine nucleotides on the melanophores of the lizard (Anolis carolinensis). Br J Pharmacol. 1969 Nov;37(3):650–658. doi: 10.1111/j.1476-5381.1969.tb08503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hilz H., Tarnowski W. Opposite effects of cyclic AMP and its dibutyryl derivative on glycogen levels in HeLa cells. Biochem Biophys Res Commun. 1970 Aug 24;40(4):973–981. doi: 10.1016/0006-291x(70)90999-x. [DOI] [PubMed] [Google Scholar]
  19. Jackson D. L. A hypothalamic region responsive to localized injection of pyrogens. J Neurophysiol. 1967 May;30(3):586–602. doi: 10.1152/jn.1967.30.3.586. [DOI] [PubMed] [Google Scholar]
  20. KLAINER L. M., CHI Y. M., FREIDBERG S. L., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. IV. The effects of neurohormones on the formation of adenosine 3',5'-phosphate by preparations from brain and other tissues. J Biol Chem. 1962 Apr;237:1239–1243. [PubMed] [Google Scholar]
  21. Kim T. S., Shulman J., Levine R. A. Relaxant effect of cyclic adenosine 3',5'-monophosphate on the isolated rabbit ileum. J Pharmacol Exp Ther. 1968 Sep;163(1):36–42. [PubMed] [Google Scholar]
  22. Kulkarni A. S. A hypothermic effect of serotonin injected into the lateral cerebral ventricle of the cat. Int J Neuropharmacol. 1967 Jul;6(4):333–335. doi: 10.1016/0028-3908(67)90024-x. [DOI] [PubMed] [Google Scholar]
  23. Laburn H. P., Rosendorff C., Willies G., Woolf C. Proceedings: A role for noradrenaline and cyclic AMP in prostaglandin E1 Fever. J Physiol. 1974 Jul;240(2):49P–50P. [PubMed] [Google Scholar]
  24. Milton A. S., Wendlandt S. A possible role for prostaglandin E1 as a modulator for temperature regulation in the central nervous system of the cat. J Physiol. 1970 Apr;207(2):76P–77P. [PubMed] [Google Scholar]
  25. Milton A. S., Wendlandt S. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol. 1971 Oct;218(2):325–336. doi: 10.1113/jphysiol.1971.sp009620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Myers R. D., Veale W. L. Body temperature: possible ionic mechanism in the hypothalamus controlling the set point. Science. 1970 Oct 2;170(3953):95–97. doi: 10.1126/science.170.3953.95. [DOI] [PubMed] [Google Scholar]
  27. Myers R. D., Yaksh T. L. Control of body temperature in the unanaesthetized monkey by cholinergic and aminergic systems in the hypothalamus. J Physiol. 1969 Jun;202(2):483–500. doi: 10.1113/jphysiol.1969.sp008822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. POSTERNAK T., SUTHERLAND E. W., HENION W. F. Derivatives of cyclic 3',5'-adenosine monophosphate. Biochim Biophys Acta. 1962 Dec 17;65:558–560. doi: 10.1016/0006-3002(62)90475-4. [DOI] [PubMed] [Google Scholar]
  29. Ryan W. L., Heidrick M. L. Inhibition of cell growth in vitro by adenosine 3',5'-monophosphate. Science. 1968 Dec 27;162(3861):1484–1485. doi: 10.1126/science.162.3861.1484. [DOI] [PubMed] [Google Scholar]
  30. Solomon S. S., Brush J. S., Kitabchi A. E. Divergent biological effects of adenosine and dibutyryl adenosine 3',5'-monophosphate on the isolated fat cell. Science. 1970 Jul 24;169(3943):387–388. doi: 10.1126/science.169.3943.387. [DOI] [PubMed] [Google Scholar]
  31. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  32. Zor U., Kaneko T., Schneider H. P., McCann S. M., Lowe I. P., Bloom G., Borland B., Field J. B. Stimulation of anterior pituitary adenyl cyclase activity and adenosine 3':5'-cyclic phosphate by hypothalamic extract and prostaglandin E1. Proc Natl Acad Sci U S A. 1969 Jul;63(3):918–925. doi: 10.1073/pnas.63.3.918. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES