In vitro and in vivo pharmacological role of TLQP-21, a VGF-derived peptide, in the regulation of rat gastric motor functions.
OBJECTIVE
Vgf gene expression has been detected in various endocrine and neuronal cells in the gastrointestinal tract. In this study we investigated the pharmacological activity of different VGF-derived peptides. Among these, TLQP-21, corresponding to the 556-576 fragment of the protein was the unique active peptide, and its pharmacological profile was further studied.


METHODS
The effects of TLQP-21 were examined in vitro by smooth muscle contraction in isolated preparations from the rat gastrointestinal tract and, in vivo, by assessing gastric emptying in rats. Rat stomach tissues were also processed for immunohistochemical and biochemical characterization.


RESULTS
In rat longitudinal forestomach strips, TLQP-21 (100 nmol x L(-1)-10 micromol x L(-1)) concentration-dependently induced muscle contraction (in female rats, EC(50) = 0.47 micromol.L(-1), E(max): 85.7 +/- 7.9 and in male rats, 0.87 micromol x L(-1), E(max): 33.4 +/- 5.3; n = 8), by release of prostaglandin (PG)E(2) and PGF(2a) from the mucosal layer. This effect was significantly antagonized by indomethacin and selective inhibitors of either cyclooxygenase-1 (S560) or cyclooxygenase-2 (NS398). Immunostaining and biochemical studies confirmed the presence of VGF in the gastric neuronal cells. TLQP-21, injected i.c.v. (2-32 nmol per rat), significantly decreased gastric emptying by about 40%. This effect was significantly (P < 0.05) blocked by i.c.v. injection of indomethacin, suggesting that, also in vivo, this peptide acts in the brain stimulating PG release.


CONCLUSIONS
The present results demonstrate that this VGF-derived peptide plays a central and local role in the regulation of rat gastric motor functions.
Severini
C
C
Institute of Neurobiology and Molecular Medicine, 00143 Rome, Italy. c.severinii@inmm.cnr.it
La Corte
G
G
Improta
G
G
Broccardo
M
M
Agostini
S
S
Petrella
C
C
Sibilia
V
V
Pagani
F
F
Guidobono
F
F
Bulgarelli
I
I
Ferri
G L
GL
Brancia
C
C
Rinaldi
A M
AM
Levi
A
A
Possenti
R
R
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology* / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C522412:TLQP-21 peptide; C522413:VGF peptide