Propranolol prevention of cholera enterotoxin-induced intestinal secretion in the rat
Donowitz, M.; Charney, A.N.
Gastroenterology 76(3): 482-491
1979
ISSN/ISBN: 0016-5085 PMID: 218865 Document Number: 149813
The ability of the .beta.-adrenergic receptor antagonist propranolol to effect intestinal secretion induced by active and passive mechanisms was evaluated in the rat ileum and colon. Ileal and colonic loops were exposed to choleragen, dibutyryl c(cyclic)AMP and hypertonic mannitol in vivo to induce water and electrolyte secretion. When studied 3.5-4.5 h after choleragen inoculation, H2O and electrolyte secretion and increased adenylate cyclase activity and cyclicAMP content were observed in intestine from untreated animals, but Na-K-ATPase, Mg-ATPase and cyclic nucleotide phosphodiesterase were unaffected. Treatment with D,L-propranolol, s.c. 4 mg/kg per day for 3 days, did not affect water or electrolyte movement or intestinal enzyme activities or cAMP content in saline-inoculated loops, but significantly reduced the choleragen-induced ileal H2O and electrolyte secretion and completely prevented the choleragen-induced colonic secretion. Propranolol treatment did not alter the choleragen-induced increase in adenylate cyclase activity or cAMP content. Similar treatment with D,L-propranolol failed to affect ileal H2O secretion induced by hypertonic mannitol. Treatment with D-propranolol, s.c. 4 mg/kg per day for 3 days, did not affect the ileal secretion induced by choleragen inoculation. To document the site of propranolol inhibition of intestinal secretion, secretion was induced by ileal perfusion with dibutyryl cAMP. Propranolol treatment completely prevented this dibutyryl cAMP-induced ileal secretion. D,L-propranolol may be able to prevent choleragen-induced ileal and colonic secretion in the rat but did not affect passive secretion caused by hypertonic mannitol. This action of propranolol is stero-specific and is not associated with inhibition of choleragen-induced activation of adenylate cyclase or increase in cAMP content and apparently involves a step in the intestinal secretory process after activation of adenylate cyclase.