Developmental regulation of gastric somatostatin secretion in the sheep

Gastric somatostatin (SRIF) regulates gastric acidity by inhibiting gastric acid and gastrin secretion. SRIF secretion is increased by gastric acidity and also directly by regulators of gastric acid secretion such as gastrin. This direct effect has not been described in the developing animal, nor ha ve the roles of intermediaries such as histamine and gastric acidity been d efined. The present study aimed to establish the regulatory role of gastrin and histamine during development on SRIF secretion and also to determine w hether the effects of gastrin and histamine are independent of gastric pH. Pentagastrin and histamine were infused on separate occasions into fetal sh eep, newborn lambs, and 28-day-old lambs. To determine the roles of endogen ous histamine and gastric pH, ranitidine (a histamine-2 receptor antagonist ) and omeprazole (a H+/K+ ATPase inhibitor) were coinfused with the agonist s. Plasma SRIF and gastrin concentrations were measured by RIA. Pentagastri n stimulated SRIF secretion in the fetus after 131 days of gestation (term is 147 days), whereas stimulation by histamine was effective only after bir th. The SRIF stimulatory effect of pentagastrin in 28-day-old lambs was abo lished by ranitidine, which also reduced this effect in the adult sheep. Th is inhibitory effect of ranitidine was shown to be a result of blockade of stimulatory H-2 receptors, because in the adult blockade of acid secretion with omeprazole failed to attenuate the response of histamine. These result s indicate that in the fetus, gastrin receptors, but not histamine receptor s, are functionally involved in the stimulation of SRIF secretion. After bi rth, both gastrin and histamine stimulate SRIF, but the effect of gastrin i s mediated at least in part by the release of endogenous histamine. These r esponses occur independently of changes in gastric acidity, supporting the concept of a direct negative feedback between SRIF and gastrin.