Octreotide inhibits increases in short-circuit current induced in rat colon by VIP, substance P, serotonin and aminophylline.
We investigated the effect of octreotide (OCT), a stable somatostatin analog, (OCT) on changes in short-circuit current (Isc) induced by vasoactive intestinal peptide (VIP), aminophylline, serotonin (5-HT) and substance P. OCT significantly decreased basal Isc at a concentration of 10(-9) M; the maximum decrease in Isc was observed at 10(-6) M. OCT (10(-7) M) significantly inhibited the intestinal secretory response to all the secretagogues studied. The maximum Isc response was reduced when tissues were stimulated with VIP (184.9 +/- 18.0 vs. 119.7 +/- 14.1, P less than 0.05), 5-HT (135.1 +/- 14.4 vs. 79.5 +/- 13.4, P less than 0.05) and substance P (156.0 +/- 19.2 vs. 30.7 +/- 5.4, P less than 0.01). In the case of aminophylline, the concentration-response curve was shifted to the right but the maximum response was not reduced. Because VIP and aminophylline increase cAMP while 5-HT and substance P stimulate intestinal secretion principally by a calcium linked mechanism, we conclude that OCT inhibits Isc in rat colon by more than one mechanism.
Department of Internal Medicine, Ohio State University, Columbus.
J E
JE
Fassler
T M
TM
O'Dorisio
H S
HS
Mekhjian
T S
TS
Gaginella
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000628:Aminophylline; D012701:Serotonin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015282:Octreotide