Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum
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Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum. / Rasmussen, T N; Schmidt, P; Poulsen, S S; Holst, J J; Poulsen, Steen Seier.
I: Neurogastroenterology and Motility, Bind 13, Nr. 4, 01.08.2001, s. 353-359.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum
AU - Rasmussen, T N
AU - Schmidt, P
AU - Poulsen, S S
AU - Holst, J J
AU - Poulsen, Steen Seier
PY - 2001/8/1
Y1 - 2001/8/1
N2 - We studied the effect of porcine CGRP (pCGRP) in concentrations from 10(-10) to 10(-8) mol L(-1) on the motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the antrum using the isolated perfused porcine antrum as experimental model. In addition, we studied the localization of CGRP by immunohistochemistry in the porcine antrum. CGRP-immunoreactive nerve fibres were found mainly in the submucous layer and in the external muscle coat, where they were seen in all layers, and in the ganglia of the myenteric nervous plexus. The frequency of contraction was significantly and dose-dependently increased from a basal level of 11.8 +/- 0.5 contractions per 5 min to 24.4 +/- 3.6 contractions per 5 min at pCGRP 10(-8) mol L(-1). At this dose, the release of substance P and neurokinin A was significantly increased to 470 +/- 149% and 217 +/- 26%, respectively, compared to basal release. The effect of pCGRP was unaffected by the addition of the nonpeptide antagonists for the NK-1 (CP-99994) and NK-2 receptors (SR48968), both at 10(-6) mol L(-1), whereas atropine (10(-6) mol L(-1)) completely abolished the motor effect of pCGRP. The release of somatostatin was significantly increased by 154 +/- 15% in response to CGRP at 10(-8) mol L(-1). The release of gastrin was unaffected by pCGRP. In conclusion, pCGRP increases contractile activity in the porcine antrum, an effect that involves cholinergic mechanisms but is independent of the release of substance P and neurokinin A. in addition, pCGRP increases the release of somatostatin but has no effect on gastrin release in the isolated perfused porcine antrum.
AB - We studied the effect of porcine CGRP (pCGRP) in concentrations from 10(-10) to 10(-8) mol L(-1) on the motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the antrum using the isolated perfused porcine antrum as experimental model. In addition, we studied the localization of CGRP by immunohistochemistry in the porcine antrum. CGRP-immunoreactive nerve fibres were found mainly in the submucous layer and in the external muscle coat, where they were seen in all layers, and in the ganglia of the myenteric nervous plexus. The frequency of contraction was significantly and dose-dependently increased from a basal level of 11.8 +/- 0.5 contractions per 5 min to 24.4 +/- 3.6 contractions per 5 min at pCGRP 10(-8) mol L(-1). At this dose, the release of substance P and neurokinin A was significantly increased to 470 +/- 149% and 217 +/- 26%, respectively, compared to basal release. The effect of pCGRP was unaffected by the addition of the nonpeptide antagonists for the NK-1 (CP-99994) and NK-2 receptors (SR48968), both at 10(-6) mol L(-1), whereas atropine (10(-6) mol L(-1)) completely abolished the motor effect of pCGRP. The release of somatostatin was significantly increased by 154 +/- 15% in response to CGRP at 10(-8) mol L(-1). The release of gastrin was unaffected by pCGRP. In conclusion, pCGRP increases contractile activity in the porcine antrum, an effect that involves cholinergic mechanisms but is independent of the release of substance P and neurokinin A. in addition, pCGRP increases the release of somatostatin but has no effect on gastrin release in the isolated perfused porcine antrum.
KW - Animals
KW - Calcitonin Gene-Related Peptide
KW - Gastrins
KW - Gastrointestinal Motility
KW - Immunohistochemistry
KW - Neurokinin A
KW - Perfusion
KW - Pyloric Antrum
KW - Somatostatin
KW - Substance P
KW - Swine
M3 - Journal article
C2 - 11576394
VL - 13
SP - 353
EP - 359
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
SN - 1350-1925
IS - 4
ER -
ID: 168990