Prokineticin-1 evokes secretory and contractile activity in rat small intestine

P. R. Wade, J. M. Palmer, J. Mabus, P. R. Saunders, S. Prouty, K. Chevalier, Melanie Gareau, S. McKenney, P. J. Hornby

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. Methods RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. Key Results In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC50 = 87.8 nmol L-1) followed by a late, TTX-insensitive (EC50 = 72.4 nmol L-1) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 ± 3% of control) and fluid secretion (340 ± 90% of control) and in muscle-stripped ileal preparations increases short-circuit current (EC50 = 8.2 nmol L-1) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP4 receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). Conclusions & Inferences These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
Volume22
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

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Endocrine-Gland-Derived Vascular Endothelial Growth Factor
Small Intestine
Fluids and Secretions
Messenger RNA
Receptors, Prostaglandin E, EP4 Subtype
Thromboxane Receptors
Gastric Fundus
Prostaglandin Receptors
Piroxicam
Cyclooxygenase Inhibitors
Ion Transport
Intestinal Mucosa
Ileum
Fluorescent Antibody Technique
Smooth Muscle
Oral Administration
Mucous Membrane
Neurons
Muscles
Polymerase Chain Reaction

Keywords

  • Cyclooxygenase
  • Endocrine-gland-derived vascular endothelial growth factor
  • Enteric nervous system
  • EP4 receptor
  • Longitudinal smooth muscle
  • Mucosa ion transport
  • Prokineticin-1
  • Prostaglandin
  • Short-circuit current
  • Small intestine

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Wade, P. R., Palmer, J. M., Mabus, J., Saunders, P. R., Prouty, S., Chevalier, K., ... Hornby, P. J. (2010). Prokineticin-1 evokes secretory and contractile activity in rat small intestine. Neurogastroenterology and Motility, 22(5). https://doi.org/10.1111/j.1365-2982.2009.01426.x

Prokineticin-1 evokes secretory and contractile activity in rat small intestine. / Wade, P. R.; Palmer, J. M.; Mabus, J.; Saunders, P. R.; Prouty, S.; Chevalier, K.; Gareau, Melanie; McKenney, S.; Hornby, P. J.

In: Neurogastroenterology and Motility, Vol. 22, No. 5, 05.2010.

Research output: Contribution to journalArticle

Wade, PR, Palmer, JM, Mabus, J, Saunders, PR, Prouty, S, Chevalier, K, Gareau, M, McKenney, S & Hornby, PJ 2010, 'Prokineticin-1 evokes secretory and contractile activity in rat small intestine', Neurogastroenterology and Motility, vol. 22, no. 5. https://doi.org/10.1111/j.1365-2982.2009.01426.x
Wade, P. R. ; Palmer, J. M. ; Mabus, J. ; Saunders, P. R. ; Prouty, S. ; Chevalier, K. ; Gareau, Melanie ; McKenney, S. ; Hornby, P. J. / Prokineticin-1 evokes secretory and contractile activity in rat small intestine. In: Neurogastroenterology and Motility. 2010 ; Vol. 22, No. 5.
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abstract = "Background Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. Methods RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. Key Results In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC50 = 87.8 nmol L-1) followed by a late, TTX-insensitive (EC50 = 72.4 nmol L-1) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 ± 3{\%} of control) and fluid secretion (340 ± 90{\%} of control) and in muscle-stripped ileal preparations increases short-circuit current (EC50 = 8.2 nmol L-1) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP4 receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). Conclusions & Inferences These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects.",
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T1 - Prokineticin-1 evokes secretory and contractile activity in rat small intestine

AU - Wade, P. R.

AU - Palmer, J. M.

AU - Mabus, J.

AU - Saunders, P. R.

AU - Prouty, S.

AU - Chevalier, K.

AU - Gareau, Melanie

AU - McKenney, S.

AU - Hornby, P. J.

PY - 2010/5

Y1 - 2010/5

N2 - Background Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. Methods RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. Key Results In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC50 = 87.8 nmol L-1) followed by a late, TTX-insensitive (EC50 = 72.4 nmol L-1) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 ± 3% of control) and fluid secretion (340 ± 90% of control) and in muscle-stripped ileal preparations increases short-circuit current (EC50 = 8.2 nmol L-1) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP4 receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). Conclusions & Inferences These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects.

AB - Background Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. Methods RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. Key Results In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC50 = 87.8 nmol L-1) followed by a late, TTX-insensitive (EC50 = 72.4 nmol L-1) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 ± 3% of control) and fluid secretion (340 ± 90% of control) and in muscle-stripped ileal preparations increases short-circuit current (EC50 = 8.2 nmol L-1) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP4 receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). Conclusions & Inferences These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects.

KW - Cyclooxygenase

KW - Endocrine-gland-derived vascular endothelial growth factor

KW - Enteric nervous system

KW - EP4 receptor

KW - Longitudinal smooth muscle

KW - Mucosa ion transport

KW - Prokineticin-1

KW - Prostaglandin

KW - Short-circuit current

KW - Small intestine

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