The secretion of HCO in the surface epithelial cell is one of the main defense mechanism of the gastroduodenal mucosa against acid (1). Mucus adherent to the luminal surface of the mucosa provides a zone of low turbulence (unstirred layer), allowing the development of a gradient for HCO, from the luminal side (2). Small amounts of HCO protect the mucosa againsi large amounts of acid by neutralizing H" ions that diffuse back into the mucus layer, and hence the HCO secretion is thought to play an important role in maintaining the integrity of the gastroduodenal mucosa (3, 4). Although the physiological regulation of HCO secretion involves prostaglandins (PGs) as well as neuro-humoral factors (3–7), it is thought that endogenous PGs are particularly important in the local control of this secretion. Indeed, PGH and its analogues, whether applied luminally or vascularly, stimulate duodenal HCO secretion in vivo and in vitro, in a variety of species including man and in this way may contribute to protection of the mucosa against acid-induced injury (3, 4). On the other hand, recent studies showed that the receptor activated by PGE, are pharmacologically subdivided in 4 subtypes, EP,--EP (8–10), but those mediating the HCO stimulatory action of PGE, remain t0 be much characterized.

The present study was designed to determine the EP receptor subtypes responsible for the HCO stimulatory action of PGE, in the gastroduodenal mucosa, by examining the effects of various subtype specific EP agonists on the HCO secretion in rats and by evaluating the HCO response to PGE, il knockout mice lacking EP-and EP-receptors.