Effect of Glucagon Secretin, and Vasoactive Intestinal Polypeptide on the Feline Lower Esophageal Sphincter: Mechanism's of Action

Abstract

We studied the effect of glucagon, secretin, and VIP on the feline LES as well as their mechanisms of action by pharmacologic analysis. Secretin and VIP caused relaxation, whereas glucagon caused LES contraction with all doses studied (1–80 μg/kg). The LES contraction in response to maximal doses of glucagon was two-thirds of the contraction after pentagastrin. Secretin was a weak LES inhibitor decreasing basal pressures by 25% and with relaxation only occurring after 4 and 8 clinical units/kg. In contrast, VIP was a potent inhibitor of LES pressures and its maximal dose (1 μg/kg) abolished basal pressures completely. The inhibitory action of secretin and VIP could not be antagonized by adrenergic (phentolamine and propranolol), or cholinergic (atropine and hexamethonium) antagonists or after complete LES denervation with tetrodotoxin. In contrast, the effect of glucagon was antagonized by a combination of hexamethonium and atropine, by phentolamine, by catecholamine depletion with reserpine, by TTX, or by surgical bilateral adrenalectomy. The dose of phentolamine needed to block the effect of a maximal dose of glucagon was onehalf of that required to antagonize the effect of a maximal dose of an alpha-adrenergic agonist (phenylephrine). These findings suggest that glucagon acts at the preganglionic level of the sympathetic pathway within the adrenal glands and its action appears to be mediated by humoral factors. Secretin and VIP appear to inhibit the LES circular muscle by direct action.