Central nervous system effects of arachidonic acid , PGE 2 , PGF 2 o , PGD 2 and PGI 2 on gastric secretion in the rat

The participation of certain brain areas, especially the hypothalamus and related limbic structures, in the regulation of the cephalic phase of gastric secretion has been documented (Grijalva, Lindholm & Novin, 1980). More recently, growing interest has been focused on the identification of chemical transmitters acting at these sites. As a result, a number of endogenous brain compounds, including noradrenaline, acetylcholine, y-aminobutyric acid (GABA) and certain neuropeptides in particular, have been reported to have central effects on gastric secretion in experimental animals (Tache, Vale, Rivier & Brown, 1981; Morley, Levine & Silvis, 1982). Whether or not these compounds play any physiological role in the central control of gastric secretion still remains to be determined. Prostaglandins, which are synthesized from arachidonic acid in mammalian brain, have been implicated as modulators of central neurotransmission (Wolfe, 1982). When administered to experimental animals, prostaglandins have centrallymediated effects on thermoregulation, the cardiovascular system, respiration, hypothalamic and pituitary hormone release and behaviour, as well as an anticonvulsant action (Behrman, 1979; Wolfe & Coceani, 1979; Wolfe, 1982; Sir6n, 1982). Prostaglandins of types A, E, and I are inhibitors of gastric secretion in various species including man, and until just recently it was accepted that they act peripherally, most probably at the level of the acidsecreting parietal cell (Robert, 1981). However, an additional, central site of action, was indicated by our recent findings that PGE2 inhibits gastric secretion in anaesthetized and conscious rats upon intracerebroventricular (i.c.v.) administration at doses of approximately one fiftieth of that which had to be given peripherally to obtain a similar response (Puurunen, 1983a; Puurunen, 1983b). Furthermore, i.c.v. administration of indomethacin, an inhibitor of prostaglandin biosynthesis, stimulates basal gastric secretion in anaesthetized and conscious rats and strongly enhances the stimulatory effect of insulin on gastric acid secretion in anaesthetized rats (Puurunen, 1983b; Puurunen, 1983c). These findings give rise to the suggestion that PGE2, and perhaps also other metabolites of arachidonic acid formed by cyclooxygenase in the brain, may be involved in the central control of gastric secretion. In the light of these