Nociceptin inhibits uterine contractions in term-pregnant rats by signaling through multiple pathways

A. Klukovits, K. Tekes, Ö Gündüz Çinar, S. Benyhe, A. Borsodi, B. H. Deák, J. Hajagos-Tóth, J. Verli, G. Falkay, R. Gáspár

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The actions of the endogenous peptide nociceptin (PNOC; previously abbreviated as N/OFQ) on the myometrium have not been investigated previously. Our aim was to study the presence and functional role of PNOC in the modulation of uterine contractility in pregnant rats at term. The presence of PNOC and its receptors (OPRL1; previously called NOP) in the uterus were detected by radioimmunoassay and radioligand-binding experiments. The PNOC-stimulated G protein activation was assessed by a [35S]GTPgammaS-binding technique. The effects of PNOC in uterine rings precontracted with KCl or oxytocin were also tested in vitro. Uterine levels of cAMP were measured by enzyme immunoassay. The K+ channel blockers tetraethylammonium and paxilline were used to study the role of K+ channels in mediating the uterine effects of PNOC. Both PNOC and OPRL1 were present in the uterus. PNOC revealed a maximum contraction inhibition of approximately 30%, which was increased to 40% by naloxone. Naloxone and pertussis toxin significantly attenuated the G protein-stimulating effect of PNOC. The uterine cAMP levels were elevated by PNOC and naloxone and after preincubation with pertussis toxin. Tetraethylammonium and paxilline reduced the contraction-inhibiting effect of PNOC and naloxone to approximately 10% and 15%, respectively. We presume that PNOC plays a role in regulating uterine contractility at term. Its effect is mediated partly by stimulatory heterotrimeric G (Gs) proteins coupled to OPRL1 receptors and elevated cAMP levels, and also by Ca2+- dependent K+ channels. Our results demonstrate a novel action and signaling pathway for PNOC that might be a potential drug target.

Original languageEnglish
Pages (from-to)36-41
Number of pages6
JournalBiology of Reproduction
Volume83
Issue number1
DOIs
Publication statusPublished - 2010

Fingerprint

Uterine Contraction
Naloxone
Tetraethylammonium
Pertussis Toxin
GTP-Binding Proteins
Uterus
Cyclic AMP Receptors
Guanosine 5'-O-(3-Thiotriphosphate)
Heterotrimeric GTP-Binding Proteins
Myometrium
Oxytocin
Immunoenzyme Techniques
Radioimmunoassay
Peptides
nociceptin
Pharmaceutical Preparations
paxilline

Keywords

  • Cyclic adenosine monophosphate
  • Neuropeptides
  • Pregnancy
  • Signal transduction
  • Uterus

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Nociceptin inhibits uterine contractions in term-pregnant rats by signaling through multiple pathways. / Klukovits, A.; Tekes, K.; Gündüz Çinar, Ö; Benyhe, S.; Borsodi, A.; Deák, B. H.; Hajagos-Tóth, J.; Verli, J.; Falkay, G.; Gáspár, R.

In: Biology of Reproduction, Vol. 83, No. 1, 2010, p. 36-41.

Research output: Contribution to journalArticle

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abstract = "The actions of the endogenous peptide nociceptin (PNOC; previously abbreviated as N/OFQ) on the myometrium have not been investigated previously. Our aim was to study the presence and functional role of PNOC in the modulation of uterine contractility in pregnant rats at term. The presence of PNOC and its receptors (OPRL1; previously called NOP) in the uterus were detected by radioimmunoassay and radioligand-binding experiments. The PNOC-stimulated G protein activation was assessed by a [35S]GTPgammaS-binding technique. The effects of PNOC in uterine rings precontracted with KCl or oxytocin were also tested in vitro. Uterine levels of cAMP were measured by enzyme immunoassay. The K+ channel blockers tetraethylammonium and paxilline were used to study the role of K+ channels in mediating the uterine effects of PNOC. Both PNOC and OPRL1 were present in the uterus. PNOC revealed a maximum contraction inhibition of approximately 30{\%}, which was increased to 40{\%} by naloxone. Naloxone and pertussis toxin significantly attenuated the G protein-stimulating effect of PNOC. The uterine cAMP levels were elevated by PNOC and naloxone and after preincubation with pertussis toxin. Tetraethylammonium and paxilline reduced the contraction-inhibiting effect of PNOC and naloxone to approximately 10{\%} and 15{\%}, respectively. We presume that PNOC plays a role in regulating uterine contractility at term. Its effect is mediated partly by stimulatory heterotrimeric G (Gs) proteins coupled to OPRL1 receptors and elevated cAMP levels, and also by Ca2+- dependent K+ channels. Our results demonstrate a novel action and signaling pathway for PNOC that might be a potential drug target.",
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AU - Tekes, K.

AU - Gündüz Çinar, Ö

AU - Benyhe, S.

AU - Borsodi, A.

AU - Deák, B. H.

AU - Hajagos-Tóth, J.

AU - Verli, J.

AU - Falkay, G.

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