Functional and immunocytochemical evidence that galanin is a physiological regulator of human jejunal motility

András Bálint, E. Fehér, István Kisfalvi, Miklós Máté, T. Zelles, E. Vízi, G. Varga

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The neuropeptide galanin has species-dependent effects on intestinal motility. It has a contractile effect on rat jejunal muscle while it relaxes guinea-pig ileum by inhibiting cholinergic transmission. Its effect on human gut motility has been unknown. Extensive work led to the discovery of selective galanin analogues such as M15 [galanin(1-12)-Pro-substance-P(5-11)], M35 [galanin(1-12)-Pro-bradykinin(2-9)-amide] that competitively inhibit various actions of galanin in the central nervous system. The present study was designed to examine the effect of galanin, M15 and M35 on longitudinal jejunal smooth muscle strips isolated from humans and rats, and to localize galanin-immunoreactivity in human jejunum. Galanin and ACh were equally effective in stimulating contractions of the isolated jejunal muscle: sigmoid curve fitting showed that maximal contractile response to galanin and ACh were 25.7±11.1 mN and 23.7±9.7 in humans, while 8.0±0.6 and 8.14-0.3 mN in rats, respectively. These effects of galanin were not inhibited by either atropine (5×10-6 M) or tetrodotoxin (3×10-6 M). The potency of galanin inducing the contractile actions were similar in humans and rats. Interestingly, neither M15 nor M35 (up to 10-7 M) were able to inhibit the responses of the smooth muscle to galanin. However, both putative galanin receptor antagonists showed agonist effects in our experimental models. In accordance with the functional studies, both the longitudinal and the circular muscle layers were abundant in nerve fibers and varicosities showing galanin immunoreactivity. Our data suggest that galanin is a potent physiological regulator of jejunal contractions in humans. Its action on the jejunum, however, is mediated by galanin receptors that are different from those located in the central nervous system.

Original languageEnglish
Pages (from-to)129-135
Number of pages7
JournalJournal of Physiology Paris
Volume95
Issue number1-6
DOIs
Publication statusPublished - 2001

Fingerprint

Galanin
Galanin Receptors
Jejunum
Muscles
Smooth Muscle
Central Nervous System
Gastrointestinal Motility
Tetrodotoxin
Sigmoid Colon
Neuropeptides
Atropine
Ileum
Nerve Fibers
Amides
Cholinergic Agents
Longitudinal Studies

Keywords

  • Chimeric analogues
  • Cotraction
  • Galanin
  • Gut motility
  • Jejunum
  • Receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology (medical)

Cite this

Functional and immunocytochemical evidence that galanin is a physiological regulator of human jejunal motility. / Bálint, András; Fehér, E.; Kisfalvi, István; Máté, Miklós; Zelles, T.; Vízi, E.; Varga, G.

In: Journal of Physiology Paris, Vol. 95, No. 1-6, 2001, p. 129-135.

Research output: Contribution to journalArticle

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AU - Máté, Miklós

AU - Zelles, T.

AU - Vízi, E.

AU - Varga, G.

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AB - The neuropeptide galanin has species-dependent effects on intestinal motility. It has a contractile effect on rat jejunal muscle while it relaxes guinea-pig ileum by inhibiting cholinergic transmission. Its effect on human gut motility has been unknown. Extensive work led to the discovery of selective galanin analogues such as M15 [galanin(1-12)-Pro-substance-P(5-11)], M35 [galanin(1-12)-Pro-bradykinin(2-9)-amide] that competitively inhibit various actions of galanin in the central nervous system. The present study was designed to examine the effect of galanin, M15 and M35 on longitudinal jejunal smooth muscle strips isolated from humans and rats, and to localize galanin-immunoreactivity in human jejunum. Galanin and ACh were equally effective in stimulating contractions of the isolated jejunal muscle: sigmoid curve fitting showed that maximal contractile response to galanin and ACh were 25.7±11.1 mN and 23.7±9.7 in humans, while 8.0±0.6 and 8.14-0.3 mN in rats, respectively. These effects of galanin were not inhibited by either atropine (5×10-6 M) or tetrodotoxin (3×10-6 M). The potency of galanin inducing the contractile actions were similar in humans and rats. Interestingly, neither M15 nor M35 (up to 10-7 M) were able to inhibit the responses of the smooth muscle to galanin. However, both putative galanin receptor antagonists showed agonist effects in our experimental models. In accordance with the functional studies, both the longitudinal and the circular muscle layers were abundant in nerve fibers and varicosities showing galanin immunoreactivity. Our data suggest that galanin is a potent physiological regulator of jejunal contractions in humans. Its action on the jejunum, however, is mediated by galanin receptors that are different from those located in the central nervous system.

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