Relation between cholecystokinin and antral innervation in the control of gastric emptying in the rat.
BACKGROUND
Antral motility and the hormone cholecystokinin (CCK) are major determinants of the rate of gastric emptying. The relation between CCK and antral neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAC) causes selective lesions in gut myenteric neurons after serosal application.


OBJECTIVE
To develop a model of antral denervation using BAC to enable the study of the relation between CCK and antral neurons in regulating gastric emptying.


METHODS
BAC, vehicle or the afferent neurotoxin capsaicin were applied to the serosal surface of the rat antrum or corpus; neurochemical markers of intrinsic and afferent neurons were detected by using immunohistochemistry and radioimmunoassay. Gastric retention of solids was determined after fasting, and emptying of liquids was measured in rats with gastric fistulae.


RESULTS
In BAC treated rats radioimmunoassay of tissue extracts revealed a dose related specific loss of gastrin releasing peptide, substance P, and vasoactive intestinal polypeptide immunoreactivities from the treated region, and immunohistochemistry revealed loss of the neuronal marker PGP 9.5 and the afferent neuropeptide calcitonin gene related peptide (CGRP). Adjacent untreated regions were unaffected by BAC, with the exception that CGRP was depleted in both corpus and antrum after antral treatment. After antral BAC treatment fasted rats retained solids for over 48 hours. Moreover, in antrally denervated rats with gastric fistulae, the emptying of saline, acid and peptone was delayed substantially. The CCK dependent inhibition of gastric emptying of peptone was preserved after antral treatment with BAC.


CONCLUSIONS
Serosal BAC causes lesions in the innervation of the treated region of the stomach. The innervation of the antrum is essential for normal emptying of both liquids and solids, but the inhibition of gastric emptying produced by CCK is not dependent on antral neurons.
Higham
A
A
Physiological Laboratory, University of Liverpool.
Vaillant
C
C
Yegen
B
B
Thompson
D G
DG
Dockray
G J
GJ
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D003714:Denervation / Q000379:methods*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D009479:Neuropeptides / Q000032:analysis; D011706:Pyloric Antrum / Q000737:chemistry / Q000187:drug effects / Q000294:innervation*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D001548:Benzalkonium Compounds; D009479:Neuropeptides; D002766:Cholecystokinin; D002211:Capsaicin