Paradoxical relationship between substrates and agonist-induced contractions of opossum esophageal body and sphincterin vitro

Abstract

Possible differences in the abilities of esophageal body and lower esophageal sphincter muscles to utilize substrates to support agonist-induced contractions were studied. Strips of longitudinal, circular, and lower esophageal sphincter muscle from the opossum esophagus were first contracted to approximately 70% of the maximal contraction elicited by acetylcholine, histamine, or substance P. The tissues were then exhausted by exposure to 5×10⁻⁴ M carbachol and a 15% O₂-5% CO₂-80% N₂ gas mixture for 90 min. They were next reequilibrated with one of a number of alternative substrates and 95% O₂-5% CO₂ for 3 hr. Responses to the initial agonist doses were again noted and compared to controls. The alternative substrates were: 2-deoxyglucose, glucose, fructose 1–6 diphosphate, pyruvate, lactate, acetate, butyrate, caprylate, histidine, leucine, aspartate, alanine, succinate, acetoacetone, and β-hydroxybutyrate. The results obtained show qualitative differences in the ability of the three muscle types to use these substrates. More importantly, however, the ability of any one substrate to support contractions was a function of the agonist used to stimulate the muscle. The evidence suggests, therefore, that not all pharmacologic receptors have equal access to intracellular energy sources.