# NO-synthase inhibitors induce a transient contraction of guinea pig ileum by a substance P dependent "non-neurokinin" receptor mechanism

Rafael Garcia Villar, Christelle Dupuis, Jean Fioramonti, Lionel Bueno

<figure><img src="image_1.png" /></figure>

## To cite this version:

Rafael Garcia Villar, Christelle Dupuis, Jean Fioramonti, Lionel Bueno. NO-synthase inhibitors induce a transient contraction of guinea pig ileum by a substance P dependent "non-neurokinin" receptor mechanism. 1st Eur Congress of Pharmacology, Jun 1995, Milan, Italy. pp.P#249. hal-01600589

HAL Id: hal-01600589

https://hal.science/hal-01600589

Submitted on 7 Jun 2020

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>
<figure><img src="image_3.png" /></figure>

PLEASE TURN OVER FOR INSTRUCTIONS

EPHAR

Federation of European Pharmacological Societies

Affiliate Member of IUPHAR

FIRST EUROPEAN CONGRESS
OF PHARMACOLOGY

Milan, Italy - June 16-19, 1995

ABSTRACT FORM to be sent by February 20, 1995 to:
EPHAR '95
FONDAZIONE GIOVANNI LORENZINI
MEDICAL SCIENCE FOUNDATION
Via Appiani, 7 - 20121 Milan (Italy)

PLEASE TYPE WITHIN
THE BLUE BOX

NO-SYNTHASE INHIBITORS INDUCE A TRANSIENT
CONTRACTION OF GUINEA PIG ILEUM BY A SUBSTANCE P-
DEPENDENT "NON-NEUROKININ" RECEPTOR MECHANISM
R. Garcia-Villar, C. Dupuis, J. Fioramonti & L. Buéno
INRA, Department of Pharmacology, BP.3, 31931, Toulouse, France.

Both substance P (SP) and nitric oxide (NO) are described respectively as activatory and inhibitory transmitters of the non-adrenergic non-cholinergic (NANC) control of gut motility. In a previous work we demonstrated that a NO-synthase (NOS) was specifically activated by SP in guinea pig ileum, but the neurokinin (NK) receptor subtype (NK1, -2, -3) involved in this activation was not precised. The present study was aimed at identifying these receptors.

**Methods:** Longitudinal strips of guinea pig ileum (8 x 2 mm) were superfused in vitro (Krebs, 37°C, 2 ml/min) with tachykinin agonists (0.1 to 10 µM; SP, GR 73,632 [NK1], GR 64,349 [NK2], senktide [NK3]), and antagonists (1µM; CP 99,941 [NK1], SR 48,968 [NK2]), SR 142,801 [NK3], as well as KCl (60 mM). NO-related agents used were L-NAME, L-NMMA, aminoguanidine (AG), L-arginine (L-ARG), D-arginine (D-ARG), sodium nitroprusside (SN) and methemoglobin (MH). Isometric contractions were recorded and quantified.

**Results:** SP and NK-receptor agonists (0.1-10 µM) produced concentration-dependent contractions of ileum strips. NOS inhibitors L-NAME, L-NMMA and AG (1 µM), superfused before any contractile agent, failed to affect muscle strip contractility. In contrast, when superfused 10 min after SP (0.1µM), they induced a transient contraction (40-70 s) of high amplitude (78±11% compared to KCl 60 mM, n=30). This contractile response was not obtained in strips stimulated by any NK-agonist (up to 10 µM), or KCl (60 mM), instead of SP. Furthermore, NK-antagonists (1 µM) did not prevent the contraction induced by NOS-inhibitors (1 µM) after SP. This response was prevented by L-ARG but not by D-ARG (1 µM), but also by both the NO donor SN (1µM) and the NO scavenger MH (10 µg/ml).

**Conclusion:** Substance P, through a mechanism which does not involve "classical" NK1-, NK2- or NK3-receptors, enables NOS inhibitors to contract the guinea pig ileum in vitro. This is likely to be achieved by blockade of SP-induced NO production, unveiling an underlying contractile state whose origin is unknown.

SELECTED TOPIC TITLE AND NUMBER (see Newsletter):

(please refer to the *List of topics for contributed papers*)

(1) **NANC** *Mediators* ☐ 1 / 2,2

(2) **NO-Synthesis inhibitors** ☐ 6 / 1

(3) **Tacky Kruis** ☐ 5 / 14

PRESENTATION PREFERENCE (CHECK ONE ONLY)

☐ Oral ☐ Poster ☑ Read by title ☑ Different

If your first choice is unavailable, you will

☑ Willingly accept alternative

☐ Withdraw the abstract

☐ Grudgingly accept alternative

Preferences will not be binding on the

Program Committee

ABSTRACTS WILL BE PUBLISHED IN A REDUCED FORM (70%) AS TYPED
EPHAR

Federation of European Pharmacological Societies
Affiliate Member of IUPHAR

# FIRST EUROPEAN CONGRESS OF PHARMACOLOGY

Milan, Italy - June 16-19, 1995

Dr. Rafael GARCIA-VILLAR
INRA
Pharmacology-Toxicology Lab.
180 Chemin de Tournefeuille
BP 3
31931 TOULOUSE
FRANCE

Chairmen

W.C. Bowman (UK)

G. Fillion (France)

H. Scholz (Germany)

H.A.J. Struijker-Boudier (The Netherlands)

R. Paoletti (Italy)

Scientific Secretaries

F. Cattabeni (Italy)

M.P. Abbracchio (Italy)

Milan, April 10, 1995

## EXPRESS MAIL

Ref.: Your submitted abstract
"NO-SYNTHASE INHIBITORS INDUCE A TRANSIENT CONTRACTION OF GUINEA..."

Dear Dr. GARCIA-VILLAR,

on behalf of the Scientific Program Committee we are pleased to
inform you that your contributed paper has been accepted for **POSTER** **presentation**.

Your **poster** has been scheduled on **Saturday, June 17, 1995** in the session "GASTROINTESTINAL PHARMACOLOGY: MOTILITY".

Each poster session will have a duration of **one day**.

For your better information please refer to the enclosed
instructions sheet.

We wish to remind you that no paper can be presented without
having paid the corresponding fee; therefore, if you have not paid
your **registration fee** yet, please do so immediately.

In case you could not attend the Congress please notify us
promptly.

With our best regards.

Yours sincerely,

Dr. Maria Pia ABBRACCHIO
(Scientific Secretary of the
Congress)

Prof. Flaminio CATTABENI
(Scientific Secretary of the
Congress)

Encl.