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 cAMP, and hypertonic mannitol in vivo to induce water and electrolyte secretion. When studied 3.5-4.5 hr after choleragen inoculation, water and electrolyte secretion and increased adenylate cyclase activity and cyclic AMP 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, SC 4 mg/kg/ day for 3 days, did not affect water or electrolyte movement or intestinal enzyme activities or cyclic AMP content in saline-inoculated loops, but significantly reduced the choleragen-induced ileal water 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 cyclic AMP content. Similar treatment with D,L-propranolol failed to affect ileal water secretion induced by hypertonic mannitol. Treatment with D-propranolol, SC 4 mg/kg/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. These results indicate that D,L-propranolol is able to prevent choleragen-induced ileal and colonic secretion in the rat but does not affect passive secretion caused by hypertonic mannitol. This action of propranolol is stereo-specific and is not associated with inhibition of choleragen-induced activation of adenylate cyclase or increase in cyclic AMP content and apparently involves a step in the intestinal secretory process after activation of adenylate cyclase.
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