Influence of atrial natriuretic peptide on mammalian large intestine.

Atrial natriuretic peptide is distributed in a number of organs including the large intestine. Atrial natriuretic peptide has potent diuretic and natriuretic properties and appears to play a central role in fluid and electrolyte homeostasis by an action on the kidney. We examined the influence of atrial natriuretic peptide on mammalian colon because this organ is also intimately involved in homeostasis. Segments of the distal colons of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. Atrial natriuretic peptide, when added to the serosal side of the mucosa, in concentrations ranging from 10(-8)-10(-5) M, caused a rapid, concentration-dependent increase in short-circuit current, transmucosal electrical potential difference, and conductance. The response to atrial natriuretic peptide was inhibited by (a) chloride-free solution on the serosal surface; (b) pretreatment of the tissues with the chloride channel blocker, diphenylamine-2-carboxylate (10(-3) M mucosally); (c) pretreatment with d,l-verapamil (10(-4) M mucosally and serosally); (d) calcium-free solution on the serosal surface; (e) pretreatment with tetrodotoxin (10(-7) M to serosal surface); and (f) pretreatment with atropine (10(-5) M serosally). However, the response to atrial natriuretic peptide was not influenced by pretreatment with amiloride (10(-4) M to mucosal and serosal surfaces) or piroxicam (10(-5) M serosally). Atrial natriuretic peptide did not elicit an increase in short-circuit current and potential difference across T84 cells derived from a human colonic carcinoma cell line, suggesting that the response to atrial natriuretic peptide is not due to a direct effect on colonocytes. These findings suggest that atrial natriuretic peptide acts by a calcium-mediated secretory mechanism involving cholinergic nerves and is likely to be involved in the endogenous neurohumoral regulation of ion transport in the mammalian colon.