The Inhibitory Effect of Cyclic 3',5' Adenosine Monophosphate and Putrescine in Inflammation

Abstract

1. The adenylate cyclase activators (salbutamol, isoprenaline and sodium phenobarbitone) were effective in inhibiting the carrageenan-induced oedema in rats, with isoprenaline being the most anti-inflammatory. 2. Isoprenaline was short-acting and significantly inhibited the carrageenan oedema only at 3 hours after the injection of carrageenan. Salbutamol significantly inhibited the carrageenan oedema at both 3 and 5 hours after carrageenan injection. 3. The anti-inflammatory effect of the B-adrenergic agonists, isoprenaline and salbutamol were inhibited by the B-adrenergic antagonist, propranolol. 4. The anti-inflammatory effect of the B-agonists coincided with the increase in plasma cyclic AMP level in rats measured at 34 hours and 54 hours after being given the drugs. 5. The phosphodiesterase inhibitor, 3-isobutyl-l-methyl xanthine was also anti-inflammatory in the carrageenan oedema. 6. DL- &-difluoromethyl ornithine, an irreversible inhibitor of ornithine decarboxylase, prevented the isoprenaline inhibition of carrageenan oedema by about 11%, suggesting the involvement of putrescine in the anti-inflammatory effect of isoprenaline. 7. Theophylline and salbutamol both inhibited the development of adjuvant arthritis in the rats. 8. The putrescine level in the theophylline-treated adjuvant rats killed on day 26 was twice that of the controls. 9. Putrescine inhibited the carrageenan oedema when injected together with carrageenan into the hind paw of the rats. 10. Putrescine also inhibited serotonin-induced oedema in the rats. 11. Putrescine was also shown to scavenge superoxide anions generated from the stimulation of guinea-pig polymorphonuclear leucocytes by N-formyl-methionyl-leucyl-phenylalaine (FMLP). 12. Putrescine failed to inhibit the development of granuloma in the cotton pellet test. 13. 1,3 diaminopropane was shown to be anti-inflammatory in the carrageenan oedema but not 1,2 diaminoethane. 14. Anti-inflammatory effect of drugs that raise cyclic AMP level may be due to cyclic AMP and polyamines.