In vitro effects of the long-acting somatostatin analogue SMS 201-995 on electrolyte transport by the rabbit ileum.

We have investigated the in vitro properties of SMS 201-995, a long-acting somatostatin analogue, on electrolyte transport in rabbit ileum. Similar to native somatostatin, serosal addition of this compound inhibits electrogenic anion secretion and stimulates neutral sodium and chloride absorption. Both compounds have similar maximal effects on ion transport; however, the ED50 of SMS 201-995 (2.4 X 10(-10) M) was 60 times less than that for somatostatin. In addition, unlike somatostatin, no inherent tachyphylaxis was observed in response to SMS 201-995. The antisecretory profile of SMS 201-995 was also compared with that of epinephrine. Unlike treatment with epinephrine, pretreatment of tissues with SMS 201-995 did not directly inhibit electrogenic anion secretion stimulated by vasoactive intestinal polypeptide, calcium ionophore A23187, and bethanechol. In contrast, this agent blocked vasoactive intestinal polypeptide and bethanechol inhibition of net sodium absorption. We conclude that SMS 201-995 has several unique in vitro properties that may explain its greater biologic activity compared with that of somatostatin. Its effects on secretagogue-stimulated electrogenic anion secretion and electroneutral NaCl absorption appear to differ.