Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct

Riccardo Patacchini, Roberto De Giorgio, L. Barthó, Giovanni Barbara, Roberto Corinaldesi, Carlo Alberto Maggi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

1. Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct pretreated with atropine (1 μM), produced a slowly-developing contraction ('on' response) followed by a quick phasic 'off' contraction ('off peak' response) and a tonic response ('off late' response), averaging 16 ± 2, 73 ± 3 and 20 ± 4% of the maximal contraction to KCl (80 mM), n = 20 each, respectively. Tetrodotoxin (1 μM; 15 min before) abolished the overall response to EFS (n = 8). 2. Neither in vitro capsaicin pretreatment (10 μM for 15 min), nor guanethidine (3 μM, 60 min before) affected the excitatory response to EFS (n = 5 each), showing that neither primary sensory neurons, nor sympathetic nerves were involved. N(ω)-nitro-L-arginine (L-NOARG, 100 μM, 60 min before) or naloxone (10 μM, 30 min before) significantly enhanced the 'on' response (294 ± 56 and 205 ± 25% increase, respectively; n = 6-8, P <0.01) to EFS. The combined administration of L-NOARG and naloxone produced additive enhancing effects (655 ± 90% increase of the 'on' component, n = 6, P <0.05). 3. The tachykinin NK2 receptor-selective antagonist MEN 11420 (1 μM) almost abolished both the 'on' and 'off late' responses (P <0.01; n = 5 each) to EFS, and reduced the 'off-peak' contraction by 55 ± 8% (n = 5, P <0.01). The subsequent administration of the tachykinin NK1 receptor-selective antagonist GR 82334 (1 μM) and of the tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence of MEN 11420 (1 μM) did not produce any further inhibition of the response to EFS (P > 0.05; n = 5 each). At 3 μM, GR 82334 significantly reduced (by 68 ± 9%, P <0.05, n = 6) the 'on' response to EFS. 4. The contractile 'off peak' response to EFS observed in the presence of both MEN 11420 and GR 82334 (3 μM each) was abolished (P <0.01; n = 6) by the administration of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM). PPADS (30 μM) selectively blocked (75 ± 9 and 50 ± 7% inhibition, n = 4 each) the contractile responses produced by 100 and 300 μM ATP. 5. Tachykinin-containing nerve fibres were detected by using immunohistochemical techniques in all parts of the bile duct, being distributed to the muscle layer and lamina propria of mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells were observed. 6. In conclusion, this study shows that in the guinea-pig terminal biliary tract tachykinins, released from intrinsic neuronal elements, are the main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2 (and possibly NK1) receptors. ATP is also involved as excitatory neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators in this preparation.

Original languageEnglish
Pages (from-to)1703-1711
Number of pages9
JournalBritish Journal of Pharmacology
Volume124
Issue number8
DOIs
Publication statusPublished - 1998

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Tachykinins
Common Bile Duct
Neurotransmitter Agents
Guinea Pigs
Purinergic P2 Receptor Antagonists
Mucous Membrane
Adenosine Triphosphate
Guanethidine
Nitroarginine
Capsaicin
Tetrodotoxin
Biliary Tract
Sensory Receptor Cells
Naloxone
Bile Ducts
Atropine
Nerve Fibers
Ganglia
Opioid Analgesics
Electric Stimulation

Keywords

  • ATP
  • Biliary tract
  • Endogenous opioids
  • Guinea-pig common bile duct
  • Nitric oxide
  • Tachykinin receptor antagonists
  • Tachykinin receptors
  • Tachykinins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct. / Patacchini, Riccardo; De Giorgio, Roberto; Barthó, L.; Barbara, Giovanni; Corinaldesi, Roberto; Maggi, Carlo Alberto.

In: British Journal of Pharmacology, Vol. 124, No. 8, 1998, p. 1703-1711.

Research output: Contribution to journalArticle

Patacchini, Riccardo ; De Giorgio, Roberto ; Barthó, L. ; Barbara, Giovanni ; Corinaldesi, Roberto ; Maggi, Carlo Alberto. / Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct. In: British Journal of Pharmacology. 1998 ; Vol. 124, No. 8. pp. 1703-1711.
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T1 - Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct

AU - Patacchini, Riccardo

AU - De Giorgio, Roberto

AU - Barthó, L.

AU - Barbara, Giovanni

AU - Corinaldesi, Roberto

AU - Maggi, Carlo Alberto

PY - 1998

Y1 - 1998

N2 - 1. Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct pretreated with atropine (1 μM), produced a slowly-developing contraction ('on' response) followed by a quick phasic 'off' contraction ('off peak' response) and a tonic response ('off late' response), averaging 16 ± 2, 73 ± 3 and 20 ± 4% of the maximal contraction to KCl (80 mM), n = 20 each, respectively. Tetrodotoxin (1 μM; 15 min before) abolished the overall response to EFS (n = 8). 2. Neither in vitro capsaicin pretreatment (10 μM for 15 min), nor guanethidine (3 μM, 60 min before) affected the excitatory response to EFS (n = 5 each), showing that neither primary sensory neurons, nor sympathetic nerves were involved. N(ω)-nitro-L-arginine (L-NOARG, 100 μM, 60 min before) or naloxone (10 μM, 30 min before) significantly enhanced the 'on' response (294 ± 56 and 205 ± 25% increase, respectively; n = 6-8, P <0.01) to EFS. The combined administration of L-NOARG and naloxone produced additive enhancing effects (655 ± 90% increase of the 'on' component, n = 6, P <0.05). 3. The tachykinin NK2 receptor-selective antagonist MEN 11420 (1 μM) almost abolished both the 'on' and 'off late' responses (P <0.01; n = 5 each) to EFS, and reduced the 'off-peak' contraction by 55 ± 8% (n = 5, P <0.01). The subsequent administration of the tachykinin NK1 receptor-selective antagonist GR 82334 (1 μM) and of the tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence of MEN 11420 (1 μM) did not produce any further inhibition of the response to EFS (P > 0.05; n = 5 each). At 3 μM, GR 82334 significantly reduced (by 68 ± 9%, P <0.05, n = 6) the 'on' response to EFS. 4. The contractile 'off peak' response to EFS observed in the presence of both MEN 11420 and GR 82334 (3 μM each) was abolished (P <0.01; n = 6) by the administration of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM). PPADS (30 μM) selectively blocked (75 ± 9 and 50 ± 7% inhibition, n = 4 each) the contractile responses produced by 100 and 300 μM ATP. 5. Tachykinin-containing nerve fibres were detected by using immunohistochemical techniques in all parts of the bile duct, being distributed to the muscle layer and lamina propria of mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells were observed. 6. In conclusion, this study shows that in the guinea-pig terminal biliary tract tachykinins, released from intrinsic neuronal elements, are the main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2 (and possibly NK1) receptors. ATP is also involved as excitatory neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators in this preparation.

AB - 1. Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct pretreated with atropine (1 μM), produced a slowly-developing contraction ('on' response) followed by a quick phasic 'off' contraction ('off peak' response) and a tonic response ('off late' response), averaging 16 ± 2, 73 ± 3 and 20 ± 4% of the maximal contraction to KCl (80 mM), n = 20 each, respectively. Tetrodotoxin (1 μM; 15 min before) abolished the overall response to EFS (n = 8). 2. Neither in vitro capsaicin pretreatment (10 μM for 15 min), nor guanethidine (3 μM, 60 min before) affected the excitatory response to EFS (n = 5 each), showing that neither primary sensory neurons, nor sympathetic nerves were involved. N(ω)-nitro-L-arginine (L-NOARG, 100 μM, 60 min before) or naloxone (10 μM, 30 min before) significantly enhanced the 'on' response (294 ± 56 and 205 ± 25% increase, respectively; n = 6-8, P <0.01) to EFS. The combined administration of L-NOARG and naloxone produced additive enhancing effects (655 ± 90% increase of the 'on' component, n = 6, P <0.05). 3. The tachykinin NK2 receptor-selective antagonist MEN 11420 (1 μM) almost abolished both the 'on' and 'off late' responses (P <0.01; n = 5 each) to EFS, and reduced the 'off-peak' contraction by 55 ± 8% (n = 5, P <0.01). The subsequent administration of the tachykinin NK1 receptor-selective antagonist GR 82334 (1 μM) and of the tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence of MEN 11420 (1 μM) did not produce any further inhibition of the response to EFS (P > 0.05; n = 5 each). At 3 μM, GR 82334 significantly reduced (by 68 ± 9%, P <0.05, n = 6) the 'on' response to EFS. 4. The contractile 'off peak' response to EFS observed in the presence of both MEN 11420 and GR 82334 (3 μM each) was abolished (P <0.01; n = 6) by the administration of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 μM). PPADS (30 μM) selectively blocked (75 ± 9 and 50 ± 7% inhibition, n = 4 each) the contractile responses produced by 100 and 300 μM ATP. 5. Tachykinin-containing nerve fibres were detected by using immunohistochemical techniques in all parts of the bile duct, being distributed to the muscle layer and lamina propria of mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells were observed. 6. In conclusion, this study shows that in the guinea-pig terminal biliary tract tachykinins, released from intrinsic neuronal elements, are the main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2 (and possibly NK1) receptors. ATP is also involved as excitatory neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators in this preparation.

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KW - Endogenous opioids

KW - Guinea-pig common bile duct

KW - Nitric oxide

KW - Tachykinin receptor antagonists

KW - Tachykinin receptors

KW - Tachykinins

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