Abstract
Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) but not by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre-treatment of the preparations with Nω-nitro-l-arginine methyl ester (l-NAME) (300 μM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 μM), apamin (0.1 μM) or tetrodotoxin (TTX) (1 μM). The results suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.
| Original language | English |
|---|---|
| Pages (from-to) | 42-47 |
| Number of pages | 6 |
| Journal | Regulatory Peptides |
| Volume | 130 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Aug 15 2005 |
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Keywords
- CGA-derived peptides
- Chromogranin A
- Intestinal smooth muscle
- Nitric oxide
- Vasostatin-1
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Neuroscience(all)
Cite this
Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the spontaneous contractions of rat proximal colon. / Amato, Antonella; Corti, Angelo; Serio, Rosa; Mulè, Flavia.
In: Regulatory Peptides, Vol. 130, No. 1-2, 15.08.2005, p. 42-47.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the spontaneous contractions of rat proximal colon
AU - Amato, Antonella
AU - Corti, Angelo
AU - Serio, Rosa
AU - Mulè, Flavia
PY - 2005/8/15
Y1 - 2005/8/15
N2 - Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) but not by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre-treatment of the preparations with Nω-nitro-l-arginine methyl ester (l-NAME) (300 μM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 μM), apamin (0.1 μM) or tetrodotoxin (TTX) (1 μM). The results suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.
AB - Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) but not by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre-treatment of the preparations with Nω-nitro-l-arginine methyl ester (l-NAME) (300 μM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 μM), apamin (0.1 μM) or tetrodotoxin (TTX) (1 μM). The results suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.
KW - CGA-derived peptides
KW - Chromogranin A
KW - Intestinal smooth muscle
KW - Nitric oxide
KW - Vasostatin-1
UR - http://www.scopus.com/inward/record.url?scp=22044446261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22044446261&partnerID=8YFLogxK
U2 - 10.1016/j.regpep.2005.03.004
DO - 10.1016/j.regpep.2005.03.004
M3 - Article
VL - 130
SP - 42
EP - 47
JO - Regulatory Peptides
JF - Regulatory Peptides
SN - 0167-0115
IS - 1-2
ER -