The vagus regulates histamine mobilization from rat stomach ECL cells by controlling their sensitivity to gastrin.
The ECL cells in the oxyntic mucosa secrete histamine in response to gastrin, stimulating parietal cells to produce acid. Do they also operate under nervous control? The present study examines histamine mobilization from rat stomach ECL cells in situ in response to acute vagal excitation and to food or gastrin following vagal or sympathetic denervation. Applying the technique of microdialysis, we monitored the release of histamine by radioimmunoassay. Microdialysis probes were placed in the submucosa on either side of the stomach, 3 days before experiments. The rats were awake during microdialysis except when subjected to electrical vagal stimulation. One-sided electrical vagal stimulation raised serum gastrin and mobilized gastric histamine. However, gastrin receptor blockade prevented the histamine mobilization, indicating that circulating gastrin accounts for the response. Vagal excitation by hypoglycaemia (insulin) or pylorus ligation did not mobilize either gastrin or histamine. The histamine response to food was almost abolished by gastrin receptor blockade, and it was halved on the denervated side after unilateral subdiaphragmatic vagotomy. While the histamine response to a near-maximally effective dose of gastrin was unaffected by vagotomy, the response to low gastrin doses was reduced significantly. Abdominal ganglionic sympathectomy failed to affect the histamine response to either food or gastrin. In conclusion, gastrin is responsible for most of the food-evoked mobilization of ECL-cell histamine. The histamine response to electrical vagal stimulation reflects the effect of circulating gastrin rather than a direct action of the vagus on the ECL cells. Vagal denervation was accompanied by an impaired histamine response to food intake, probably reflecting the right-ward shift of the serum gastrin concentration-histamine response curve. The results suggest that the vagus controls the sensitivity of the ECL cells to gastrin.
Norlén
P
P
Department of Experimental and Clinical Pharmacology, Institute of Laboratory Medicine, Lund University Hospital, S-22185 Lund, Sweden. per.norlen@skane.se
Ericsson
P
P
Kitano
M
M
Ekelund
M
M
Håkanson
R
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019861:Enterochromaffin-like Cells / Q000187:drug effects / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D005755:Gastrins; D006632:Histamine
Digestion. 1988;40(1):25-32
3234616
Scand J Gastroenterol Suppl. 1991;180:88-94
2042038
Gut. 1991 Jun;32(6):698-701
1711995
Scand J Gastroenterol. 1992;27(1):65-70
1736345
Trends Neurosci. 1992 Feb;15(2):66-71
1374965
Gastroenterology. 1993 Aug;105(2):449-61
7687574
J Surg Res. 1995 Jan;58(1):96-104
7530310
Yale J Biol Med. 1994 May-Aug;67(3-4):145-51
7502523
Gastroenterology. 1996 Apr;110(4):1084-92
8612997
Scand J Gastroenterol. 1996 Jan;31(1):31-7
8927937
Jpn J Pharmacol. 1996 Jul;71(3):223-30
8854204
Pharmacol Toxicol. 1996 Dec;79(6):324-30
9000260
Lab Anim Sci. 1997 Jun;47(3):300-3
9241634
Cell Tissue Res. 1998 Jan;291(1):65-79
9394044
Regul Pept. 1997 Aug 15;71(2):73-86
9416989
Ann N Y Acad Sci. 1998 Dec 11;865:147-56
9928007
J Clin Invest. 1999 Nov;104(10):1383-91
10562300
Regul Pept. 2000 Jan 29;86(1-3):113-23
10672910
J Chem Soc Perkin 1. 1968;6:726-33
5688891
J Physiol. 1974 Dec;243(2):483-98
4449071
Neuroscience. 1980;5(4):689-744
6156425
J Physiol. 1980 Aug;305:139-49
7441551
J Physiol. 1982 Feb;323:145-56
7097572
Acta Physiol Scand. 1982 Jan;114(1):17-29
6182747
Acta Physiol Scand. 1982 May;115(1):135-9
7136798
Am J Physiol. 1982 Dec;243(6):G442-7
6128924
Acta Physiol Scand. 1983 Apr;117(4):491-5
6192683
Gastroenterology. 1984 Jan;86(1):28-32
6689671
Acta Physiol Scand. 1983 Sep;119(1):77-80
6650207
Surgery. 1984 Jan;95(1):34-7
6362046
Neurosci Lett. 1984 Sep 7;50(1-3):73-8
6093016
Gastroenterology. 1985 Jul;89(1):73-85
2408958
Gastroenterology. 1966 Jun;50(6):787-95
5212380
Histochemistry. 1986;86(1):5-17
2878908
Eur J Pharmacol. 1987 Jun 19;138(2):225-32
3622610
Scand J Gastroenterol. 1987 Sep;22(7):803-8
2445018
Neuroscience. 1988 Apr;25(1):181-93
2455875
Regul Pept. 1988 Aug;22(3):237-43
3175061
Br J Pharmacol. 2003 Oct;140(4):707-17
14504142
Comp Med. 2004 Jun;54(3):293-300
15253276
Neurogastroenterol Motil. 2004 Oct;16 Suppl 2:3-16
15357847
Nature. 1965 Sep 25;207(5004):1356-9
5886035
Surgery. 1967 Jan;61(1):129-35
6016660
Br J Pharmacol. 2000 Jun;130(3):699-705
10821801
Br J Pharmacol. 2000 Jun;130(4):725-30
10864877
Regul Pept. 2001 Mar 2;97(2-3):169-80
11164953
Br J Pharmacol. 2001 May;133(1):37-42
11325792
Br J Pharmacol. 2001 Dec;134(8):1767-77
11739254
Scand J Gastroenterol. 2002 Jul;37(7):750-3
12190085
Pharmacol Toxicol. 2003 Aug;93(2):57-65
12899666