Involvement of cyclic AMP in sodium transport across the gastric mucosa of the rabbit fetus

Abstract

Transepithelial ion transport across the gastric mucosa of the 28 day old rabbit fetus was studied in vitro using the short-circuit current (s.c.c.) technique of Ussing and Zerahn (1951).Addition of adenosine 3',5'-monophosphate (cyclic AMP) or its dibutyryl derivative to the short-circuited membrane preparation was immediately followed by an increase in ion transport across this membrane: administration of methyl xanthines also resulted in asimilar increase. The application of adrenaline, vasopressin, glucagon or pentagastrin was also followed by an increase in the s.c.c.Mucosal ceLL suspensions, obtained by the method of Wright and Malinowska (1978), were used to study the possible effect of various agents on the intraceL lular cyclic AMP Level. Experiments have shown that the addition of theophyLline, adrenaline or vasopressin resulted in an increase in the intracellular cyclic nucleotide Level which was followed (but not Led) by an increase in the s.c.c. These results indicate the involvement of cyclic AMP in the regulation of ion transport across the fetal stomach.Application of prostaglandin synthetase inhibitors, acetyl saLicylic acid and similar non-steroidal anti-inflammatory drugs resulted in an inhibition of ion transport across the membrane, whereas the addition of prostaglandin precursor, arachidonic acid was followed by an increase in the s.c.c. These results indicate (1) the ability of fetal stomach to synthesize prostagLandins and (2) theinvolvement of prostaglandins in the regulation of active iontransport across this membrane.Radioactive isotopes and were used to investigate the effect of theophyLline on the undirectionaI transport of sodium and chloride ions across the 28 day old gastric mucosa. Experiments have shown that the addition of theophylline resulted in a large increase in net transport of sodium in the direction of mucosa to serosa, whereas chloride transport was unaffected. Furthermore such experiments have indicated that some other ion(s) besides sodium was also stimulated by these drugs.Further experiments were carried out on intact membranepreparations to determine whether the gastric mucosa of the fetus possesses seperate adenylate cyclase system each being responsive to a single hormone only or whether both adrenaline and vasopressinincrease ion transport by stimulating a single cyclase which is common to both hormones. The response of the gastric mucosa toadrenaline was blocked by -receptor blockers, propranolol andtimolol but not by receptor blocker, phentolamine. - or-receptor blockers had no effect upon the response to vasopressin. The addition of adrenaline together with vasopressin did not result in an additive increase in the s.c.c. From these results it is concluded that the fetal gastric mucosa posseses a single commonadenylate cyclase system which is stimulated by both adrenaline andvasopressin each acting on separate receptor sites of the enzyme.