To determine whether long vagal cholinergic pathways are involved in e
rythromycin-induced pancreatic polypeptide release, erythromycin was a
dministered as an intravenous bolus injection to 9 healthy volunteers
(group A) and to 13 patients (group B) with impaired vagal function as
a result of truncal vagotomy or accidental vagotomy after antireflux
surgery. In 7 of these patients (group B-1) an antrectomy was also per
formed, while in the other 6 patients (group B-2) the antrum was not r
emoved. Pancreatic polypeptide was measured by radioimmunoassay at 5-m
in intervals twice before and at 2, 5, 10, 15, 30, 45 and 60 min after
a 3.5 mg/kg bolus injection of erythromycin. On another day, a standa
rd meal was administered and plasma pancreatic polypeptide was measure
d at 10-min intervals for 1 h. Erythromycin injection resulted in a lo
wer integrated pancreatic polypeptide response in the patients of grou
p B-1 (247 +/- 89 pmol/l x 15 min; p = 0.005) and group B-2 (497 +/- 1
11 pmol/l x 15 min; p = 0.05) when compared to the healthy subjects of
group A (1,136 +/- 227 pmol/l x 15 min). The pancreatic polypeptide r
esponse to erythromycin in group B-1 was reduced when compared to grou
p B-2, but the difference just failed to reach statistical significanc
e (0.05 < p < 0.10). In the first 30 min after ingestion of a meal (ce
phalic phase) pancreatic polypeptide release was also markedly lower i
n group B-1 (1,461 +/- 304 pmol/l x 30 min; p < 0.005) and group B-2 (
1,452 +/- 215 pmol/l x 30 min; p < 0.005) when compared to group A (3,
541 +/- 452 pmol/l x 30 min). However, in the second 30 min after inge
stion of a meal (intestinal phase), no significant difference in pancr
eatic polypeptide response was observed between group A, B-1 and group
B-2 (3,689 +/- 690 pmol/l x 30 min, 3,319 +/- 938 pmol/l x 30 min and
3,119 +/- 761 pmol/l x 30 min, respectively). These last results demo
nstrate that pancreatic polypeptide cells were functional in all patie
nts and controls. We conclude that the effect of erythromycin on pancr
eatic polypeptide release is at least in part dependent on intact long
vagal cholinergic pathways. Furthermore, preservation of the antrum s
eems to be of importance for erythromycin-induced pancreatic polypepti
de release.