Human colonic epithelial cells express galanin-1 receptors, which when activated cause Cl- secretion

Richard V. Benya, Jorge A. Marrero, Denis A. Ostrovskiy, Athanasia Koutsouris, Gail Hecht

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Galanin is a peptide hormone widely expressed in the central nervous system and gastrointestinal (GI) tract. Within the GI tract galanin is present in enteric nerve terminals where it is known to modulate intestinal motility by altering smooth muscle contraction. Recent studies also show that galanin can alter intestinal short-circuit current (I(sc)) but with differing results observed in rats, rabbits, guinea pigs, and pigs. In contrast, nothing is known about the ability of galanin to alter ion transport in human intestinal epithelial tissues. By RT-PCR, we determined that these tissues express only the galanin-1 receptor (Gall-R) subtype. To evaluate Gal1-R pharmacology and physiology, we studied T84 cells. Gal1-R expressed by these cells bound galanin rapidly (half time 1-2 min) and with high affinity (inhibitor constant 0.7 ± 0.2 nM). T84 cells were then studied in a modified Ussing chamber and alterations in I(sc), a measure of all ion movement across the tissue, were determined. Maximal increases in I(sc) were observed in a concentration-dependent manner around 2 min after stimulation with peptide, with 1 μM galanin causing I(sc) to rise more than eight-fold and return to baseline occurring within 10 min. The increase in galanin-induced I(sc) was shown by 125I efflux studies to be due to Cl- secretion, which occurred independently of alterations in cAMP and phospholipase C. Rather, Cl- secretion is mediated via a Ca2+-dependent, pertussis toxin-sensitive mechanism. These data suggest that galanin released by enteric nerves may act as a secretagogue in the human colon by activating Gal1-R.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number1 39-1
StatePublished - Jan 1999

Fingerprint

Receptor, Galanin, Type 1
Galanin
Epithelial Cells
Gastrointestinal Tract
Gastrointestinal Motility
Peptide Hormones
Ion Transport
Pertussis Toxin
Type C Phospholipases
Intestinal Mucosa
Muscle Contraction
Smooth Muscle
Guinea Pigs
Colon
Swine
Central Nervous System
Pharmacology

Keywords

  • Diarrhea
  • Pharmacology

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Human colonic epithelial cells express galanin-1 receptors, which when activated cause Cl- secretion. / Benya, Richard V.; Marrero, Jorge A.; Ostrovskiy, Denis A.; Koutsouris, Athanasia; Hecht, Gail.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 276, No. 1 39-1, 01.1999.

Research output: Contribution to journalArticle

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