In vivo inhibitory effect of lanreotide (BIM 23014), a new somatostatin analog, on prostaglandin- and cholera toxin-stimulated intestinal fluid in the rat.
The antisecretory action of subcutaneously (SC) administered somatostatin(1-14), octreotide, and lanreotide on jejunal net flux of water under basal, prostaglandin E1 (PGE1)- and cholera toxin (CT)-stimulated secretory conditions was determined in vivo on isolated intestinal loop in anesthetized rats. Both PGE1 and CT induced intestinal hypersecretion in the rats. This secretory effect was not affected by SC administration of saline. Lanreotide (1, 10, and 100 micrograms/kg) reduced the maximal PGE1-induced secretion, while 200 micrograms/kg had no effect. Similarly, octreotide (1 and 10 micrograms/kg) and somatostatin (1-14) (0.1 and 1 microgram/kg) reduced the increase of net water flux induced by PGE1. However, higher doses of octreotide (100 and 200 micrograms/kg) and somatostatin(1-14) (10 and 100 micrograms/kg) had no effect on PGE1-induced secretion. Lanreotide, octreotide, and somatostatin(1-14) (1 and 10 micrograms/kg) abolished the maximal secretion induced by cholera toxin. However, 100 micrograms/kg of lanreotide, octreotide, and somatostatin(1-14) had no effect on cholera toxin-induced secretion. The present study shows that lanreotide, octreotide, and somatostatin(1-14) reduce the secretion induced by PGE1 and abolish that induced by CT. These effects were obtained with doses of less than 100 micrograms/kg of the products, higher doses being ineffective. The higher efficacy against CT-induced hypersecretion as compared to PGE1-induced hypersecretion suggests a direct antisecretory effect at the enterocyte level and indicates the usefulness of these products as antidiarrheal agents in nonhormonally mediated diarrhea.
Botella
A
A
Department of Pharmacology, INRA, Toulouse, France.
Vabre
F
F
Fioramonti
J
J
Thomas
F
F
Bueno
L
L
D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015282:Octreotide / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D002772:Cholera Toxin; D000527:Alprostadil; D015282:Octreotide