The genesis of lower esophageal sphincter pressure: its identification through the use of gastrin antiserum.

The purpose of this study was to evaluate the role of gastrin in the genesis of lower esophageal sphincter (LES) pressure by the use of a high titer gastrin antiserum. Intravenous infusions of increasing amounts of rabbit gastrin antiserum, but not control antiserum, produced graded reductions in the resting LES pressure in anesthetized opossums. A maximal inhibition in LES pressure of 80.0+/-3.1% (mean +/-SE) was achieved when gastrin antiserum was administered in an amount estimated to bind almost all endogenous circulating gastrin in the opossum. Gastrin antiserum also inhibited the LES response to endogenous gastrin release (gastric deacidification) and to exogenous intravenous administration of gastrin I. The inhibition of the LES response to exogenous gastrin I by gastrin antiserum could be eliminated by giving excess gastrin I. Studies performed in vitro showed that gastrin antiserum inhibited the contractile response of LES circular muscle to gastrin I, but not to acetylcholine. These studies indicate that gastrin antiserum: (a) specifically antagonized the response of LES circular muscle to gastrin, in vitro; (b) diminished the LES response to the endogenous release and to the exogenous administration of gastrin; and (c) markedly reduced the resting level of LES pressure. We conclude that endogenous gastrin is the major determinant of resting LES pressure.