Secretion of pancreatic polypeptide in man in response to beef ingestion is mediated in part by an extravagal cholinergic mechanism

Abstract

The effect of atropine, a muscarinic cholinergic blocking agent, on the response of plasma pancreatic polypeptide (hPP) to the ingestion of beef was investigated. Six healthy subjects ingested 250 g broiled ground beef on three occasions. After beef ingestion alone, the expected biphasic plasma hPP response was observed. On the two other occasions atropine (intravenous bolus followed by infusion) was begun either at 4 or 60 min after the beginning of beef ingestion so as to coincide with the early (first) and late (second) phases of hPP response to beef ingestion. On both occasions plasma hPP concentrations returned rapidly to baseline. Mean integrated incremental hPP responses in the absence of atropine were 9.1 +/- 3.4 ng min ml-1 for the first phase (0-40 min) and 29.7 +/- 5.7 ng min ml-1 for the second phase (60-180 min); with atropine at 4 min, respective responses were 0.8 +/- 0.9 and -1.0 +/- 1.3 ng min ml-1, and with atropine at 60 min they were 10.6 +/- 5.0 and 1.3 +/- 1.6 ng min ml-1. After atropine administration, the half-time of disappearance of hPP from the circulation was 4-6 min, suggesting the complete cessation of stimulated hPP secretion. We conclude that the mechanisms of both the early and late phases of beef meal-stimulated release of hPP involve muscarinic cholinergic-neural transmission. The portion of the second (late) phase response which has been shown to persist after truncal vagotomy must be mediated by a cholinergic mechanism which is extravagal in character.