In vitro and in vivo pharmacological role of TLQP‐21, a VGF‐derived peptide, in the regulation of rat gastric motor functions

Severini, Cinzia; Corte, Giorgio; Improta, Giovanna; Broccardo, Maria; Agostini, Simona; Petrella, Carla; Sibilia, V.; Pagani, F.; Guidobono, F.; Bulgarelli, Ilaria; Gl, Ferri; Brancia, Carla; Am, Rinaldi; Levi, Andrea; Possenti, Roberta

doi:10.1111/j.1476-5381.2009.00192.x

Cited by 40 publications

(39 citation statements)

References 44 publications

(82 reference statements)

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“…These observations were later confirmed by a large series of studies in Siberian hamsters and mice [2,9,10,11,12,13,14]. Thereafter, different experimental studies proposed that these peptides were also involved in the control of gastrointestinal function, water balance, endocrine and exocrine pancreatic secretion, neural and pancreatic islet β-cell survival, inflammatory pain, stress responses and emotional behavior [15,16,17,18,19,20,21,22,23]. …”

Section: Introductionmentioning

confidence: 55%

Characterization of the Reproductive Effects of the Vgf-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

et al. 2013

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Background: VGF (non-acronymic), a protein expressed in the hypothalamus and pituitary, is involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Previous studies of our group reported that this molecule participates also in the regulation of reproductive function in male rats, with predominant stimulatory effects. Methods: We report herein a series of studies on the reproductive effects of TLQP-21 in female rats, as evaluated by a combination of in vivo and in vitro analyses. Results: TLQP-21 modestly increased serum LH levels after systemic administration and directly stimulated pituitary LH and FSH secretion in prepubertal female rats, while acute central injection of TLQP-21 was unable to modify LH secretion at this age. Repeated central administration of TLQP-21 during the pubertal transition (between PND-28 and -35) to female rats fed ad libitum advanced the timing of vaginal opening and increased the percentage of animals with signs of ovulation. Moreover, an analogous treatment slightly enhanced ovarian maturation in pubertal female rats subjected to chronic undernutrition, but was unable to rescue the delay of vaginal opening induced by food deprivation. In addition, TLQP-21 oppositely modified LH secretion in adult female rats depending on the stage of the ovarian cycle: it stimulated LH secretion when injected in the morning of diestrus and decreased the magnitude of the preovulatory LH (but not FSH) surge when injected in the afternoon of proestrus. Conclusions: Our data are the first to document the potential involvement of TLQP-21 in the control of reproductive function in female rats.

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Section: Introductionmentioning

confidence: 55%

Characterization of the Reproductive Effects of the Vgf-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

et al. 2013

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“…2I-J). VGF C-terminus immunoreactivity was confined to neuronal structures, including myenteric perikarya and axons in all layers of the wall, with no labelling of endocrine or other mucosal cells, as reported previously (Severini et al 2009). Nerve structures were also revealed by the VGF 443-588 antiserum (Fig.…”

Section: Immunohistochemistry and In Situ Hybridisationmentioning

confidence: 62%

“…The only VGF peptide studied so far, TLQP-21, induced gastric longitudinal muscle contraction in vivo, while inhibiting gastric emptying when given i.c.v. (Severini et al 2009). …”

Section: Discussionmentioning

confidence: 99%

“…On the whole, TLQP peptides could have a role in the regulatory machinery of the ECL cells or, upon release from ECL and/or somatostatin cells, could act locally in a paracrine manner or via neuroendocrine pathways such as those involving the vagus nerve (Dockray 2009). So far, peripheral administration of TLQP-21 proved uneffective (Jethwa et al 2007, Severini et al 2009). In the brain, TLQP-62 and TLQP-21 were suggested to have an agonist-antagonist action upon hippocampal synaptic potentiation (Bozdagi et al 2007), while the bioactivity of the additional forms we found remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

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Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

Brancia¹,

Cocco²,

D'Amato³

et al. 2010

Journal of Endocrinology

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Although vgf gene knockout mice are hypermetabolic, administration of the VGF peptide TLQP-21 itself increased energy consumption. Agonist-antagonist roles are thus suggested for different VGF peptides, and the definition of their tissue heterogeneity is mandatory. We studied the rat stomach using antisera to C-or N-terminal sequences of known or predicted VGF peptides in immunohistochemistry and ELISA. TLQP (rat VGF 556-565 ) peptide/s were most abundant (162G11 pmol/g, meanGS.E.M.) and were brightly immunostained in enterochromaffin-like (ECL) cells and somatostatin cells. A peptide co-eluting with TLQP-21 was revealed in HPLC of gastric and hypothalamic extracts, while the extended TLQP-62 form was restricted to the hypothalamus. Novel PGH (rat VGF 422-430 ) peptide/s were revealed in ghrelin cells, mostly corresponding to low MW forms (0 . 8-1 . 5 kDa), while VGF C-terminus peptides were confined to neurons. VGF mRNA was present in the above gastric endocrine cell types, and was prominent in chief cells, in parallel with low-intensity staining for further cleaved products from the C-terminal region of VGF (HVLL peptides: VGF 605-614 ). In swine stomach, a comparable profile of VGF peptides was revealed by immunohistochemistry. When fed and fasted rats were studied, a clear-cut, selective decrease on fasting was observed for TLQP peptides only (162G11 vs 74G5 . 3 pmol/g, fed versus fasted rats, meanGS.E.M., P!0 . 00001). In conclusion, specific VGF peptides appear to be widely represented in different gastric endocrine and other mucosal cell populations. The selective modulation of TLQP peptides suggests their involvement in peripheral neuro-endocrine mechanisms related to feeding responses and/or ECL cell regulation.

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“…TLQP-21 was also reported to play a role in lipolysis (8). Injection of TLQP-21 decreases gastric acid secretion (9) and gastric emptying (10) in rats. This effect was further explored by Brancia et al (11), who demonstrated that TLQP-21 is expressed in the ECL (enterochromaffin-like) and somatostatin cells of the stomach, strongly suggesting the existence of a physiological control loop.…”

mentioning

confidence: 99%

Identification of the C3a Receptor (C3AR1) as the Target of the VGF-derived Peptide TLQP-21 in Rodent Cells

Hannedouche

Beck

Leighton-Davies

et al. 2013

Journal of Biological Chemistry

115

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In vitro and in vivo pharmacological role of TLQP‐21, a VGF‐derived peptide, in the regulation of rat gastric motor functions

Cited by 40 publications

References 44 publications

Characterization of the Reproductive Effects of the <b><i>Vgf</i></b>-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

Characterization of the Reproductive Effects of the <b><i>Vgf</i></b>-Derived Peptide TLQP-21 in Female Rats: In vivo and in vitro Studies

Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

Identification of the C3a Receptor (C3AR1) as the Target of the VGF-derived Peptide TLQP-21 in Rodent Cells

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