Galanin receptor 3--a potential target for acute pancreatitis therapy

S G Barreto, M Bazargan, M Zotti, D J Hussey, O A Sukocheva, H Peiris, M Leong, D J Keating, A C Schloithe, C J Carati, C Smith, J Toouli, G T P Saccone

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Abstract

BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP.

METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h.

KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%).

CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.

Original languageEnglish
Pages (from-to)e141-51
Number of pages11
JournalJournal of Gastrointestinal Motility
Volume23
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

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Receptor, Galanin, Type 3
Galanin Receptors
Pancreatitis
Acinar Cells
Messenger RNA
Galanin
Pancreas
Ceruletide
Therapeutics
Amylases
Islets of Langerhans
In Situ Hybridization
Western Blotting
Proteins

Cite this

Barreto, S. G., Bazargan, M., Zotti, M., Hussey, D. J., Sukocheva, O. A., Peiris, H., ... Saccone, G. T. P. (2011). Galanin receptor 3--a potential target for acute pancreatitis therapy. Journal of Gastrointestinal Motility, 23(3), e141-51. https://doi.org/10.1111/j.1365-2982.2010.01662.x
Barreto, S G ; Bazargan, M ; Zotti, M ; Hussey, D J ; Sukocheva, O A ; Peiris, H ; Leong, M ; Keating, D J ; Schloithe, A C ; Carati, C J ; Smith, C ; Toouli, J ; Saccone, G T P. / Galanin receptor 3--a potential target for acute pancreatitis therapy. In: Journal of Gastrointestinal Motility. 2011 ; Vol. 23, No. 3. pp. e141-51.
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abstract = "BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP.METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h.KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80{\%}).CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.",
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Barreto, SG, Bazargan, M, Zotti, M, Hussey, DJ, Sukocheva, OA, Peiris, H, Leong, M, Keating, DJ, Schloithe, AC, Carati, CJ, Smith, C, Toouli, J & Saccone, GTP 2011, 'Galanin receptor 3--a potential target for acute pancreatitis therapy' Journal of Gastrointestinal Motility, vol. 23, no. 3, pp. e141-51. https://doi.org/10.1111/j.1365-2982.2010.01662.x

Galanin receptor 3--a potential target for acute pancreatitis therapy. / Barreto, S G; Bazargan, M; Zotti, M; Hussey, D J; Sukocheva, O A; Peiris, H; Leong, M; Keating, D J; Schloithe, A C; Carati, C J; Smith, C; Toouli, J; Saccone, G T P.

In: Journal of Gastrointestinal Motility, Vol. 23, No. 3, 03.2011, p. e141-51.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Galanin receptor 3--a potential target for acute pancreatitis therapy

AU - Barreto, S G

AU - Bazargan, M

AU - Zotti, M

AU - Hussey, D J

AU - Sukocheva, O A

AU - Peiris, H

AU - Leong, M

AU - Keating, D J

AU - Schloithe, A C

AU - Carati, C J

AU - Smith, C

AU - Toouli, J

AU - Saccone, G T P

N1 - © 2011 Blackwell Publishing Ltd.

PY - 2011/3

Y1 - 2011/3

N2 - BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP.METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h.KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%).CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.

AB - BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP.METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h.KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%).CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.

U2 - 10.1111/j.1365-2982.2010.01662.x

DO - 10.1111/j.1365-2982.2010.01662.x

M3 - Article

VL - 23

SP - e141-51

JO - Journal of Gastrointestinal Motility

JF - Journal of Gastrointestinal Motility

SN - 1350-1925

IS - 3

ER -