In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin

Florence Bétoin; Charles Advenier; Véronique Fardin; George Wilcox; Jeannine Lavarenne; Alain Eschalier

doi:10.1016/0014-2999(95)00168-K

In vitro and in vivo evidence for a tachykinin NK₁ receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin

Florence Bétoin
, Charles Advenier
, Véronique Fardin
, George Wilcox
, Jeannine Lavarenne
, Alain Eschalier

Neuroscience

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK₁ and NK₂ receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [³H]substance P (IC₅₀ = 3.3 ± 1.8 × 10^-7 M) from guinea-pig bronchial tachykinin NK₁ sites. The displacement of [¹²⁵I]neurokinin A, a specific tachykinin NK₂ receptor ligand, needed higher concentrations (IC₅₀ = 4.5 ± 0.6 × 10^-6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK₁ receptors; the involvement in its analgesic action is discussed.

Original language	English (US)
Pages (from-to)	241-249
Number of pages	9
Journal	European Journal of Pharmacology
Volume	279
Issue number	2-3
DOIs	https://doi.org/10.1016/0014-2999(95)00168-K
State	Published - Jun 12 1995

Bibliographical note

Funding Information:
This work has been supported by a grant from Debiopharm S.A. Lausanne and l'Association pour la Recherche sur le Cancer, Paris. We are grateful to C. Garret (Rh6ne-Poulenc-Rorer, Paris) for his help.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Airway
Binding
Somatostatin analog
Substance P
Tachykinin NK receptor
Tachykinin NK receptor
Vapreotide

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10.1016/0014-2999(95)00168-K

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title = "In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin",

abstract = "Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 ± 1.8 × 10-7 M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 ± 0.6 × 10-6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.",

keywords = "Airway, Binding, Somatostatin analog, Substance P, Tachykinin NK receptor, Tachykinin NK receptor, Vapreotide",

author = "Florence B{\'e}toin and Charles Advenier and V{\'e}ronique Fardin and George Wilcox and Jeannine Lavarenne and Alain Eschalier",

note = "Funding Information: This work has been supported by a grant from Debiopharm S.A. Lausanne and l'Association pour la Recherche sur le Cancer, Paris. We are grateful to C. Garret (Rh6ne-Poulenc-Rorer, Paris) for his help.",

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T1 - In vitro and in vivo evidence for a tachykinin NK1 receptor antagonist effect of vapreotide, an analgesic cyclic analog of somatostatin

AU - Bétoin, Florence

AU - Advenier, Charles

AU - Fardin, Véronique

AU - Wilcox, George

AU - Lavarenne, Jeannine

AU - Eschalier, Alain

N1 - Funding Information: This work has been supported by a grant from Debiopharm S.A. Lausanne and l'Association pour la Recherche sur le Cancer, Paris. We are grateful to C. Garret (Rh6ne-Poulenc-Rorer, Paris) for his help.

PY - 1995/6/12

Y1 - 1995/6/12

N2 - Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 ± 1.8 × 10-7 M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 ± 0.6 × 10-6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.

AB - Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [3H]substance P (IC50 = 3.3 ± 1.8 × 10-7 M) from guinea-pig bronchial tachykinin NK1 sites. The displacement of [125I]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 ± 0.6 × 10-6 M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.

KW - Airway

KW - Binding

KW - Somatostatin analog

KW - Substance P

KW - Tachykinin NK receptor

KW - Vapreotide

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