Central gastric antisecretory action of adenosine in the rat

The effects of intracerebroventricularly (i.c.v.) administered adenosine and some of its analogues on gastric secretion were studied in rats. The compounds inhibited the gastric output of acid, pepsin and fluid in pylorus-ligated rats in a dose-dependent manner with an order of potency: 5'-N-ethylcarboxamidoadenosine (NECA) greater than (-)N6-phenylisopropyladenosine (R-PIA) greater than (+)N6-phenylisopropyladenosine (S-PIA) greater than adenosine. Pretreatment with 10 and 30 mg/kg of theophylline i.v. or 5 mg/kg of 8-phenyltheophylline s.c. did not modify the antisecretory effect of 0.1 microgram of NECA i.c.v. NECA injected i.c.v. did not affect the secretion induced by carbachol in awake rats subjected to vagotomy or in anaesthetized rats with intact vagi. NECA i.c.v. had no effect on the serum concentration of gastrin. The depletion of brain monoamines (noradrenaline, dopamine and serotonin) with 6-OHDA i.c.v. significantly attenuated the inhibitory action of NECA. Pretreatment with 10 mg/kg of naloxone i.v. or indomethacin s.c. did not modify the antisecretory effect of NECA. The results indicate that adenosine inhibits gastric secretion in rats by a decrease in the stimulatory vagal impulses to the stomach, and that it acts in the brain via receptors insensitive to xanthines. Brain biogenic monoamines, but not opioid peptides or prostaglandins seem to be involved in the central gastric antisecretory action of adenosine.