Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum

J. Pablo Huidobro-Toro, César A. Chelala, Suleiman Bahouth, Robert Nodar, JoséM M. Musacchio

Research output: Contribution to journalArticle

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Abstract

Substance P (SP) caused an immediate and vigorous contraction of the longitudinal smooth muscle layer of the guinea-pig ileum. The contractile response to SP, unlike that to acetylcholine or histamine was not maintained but faded to baseline levels in about 6 min. When 0.3-1.0 nM SP was added the fading time was shorter than 6 min and tachyphylaxis did not develop. Higher concentrations of SP produced fading times of about 6 min that could not be increased even by adding extremely high concentrations of the peptide, up to 1 800 nM. Short fading timesand the lack of development of tachyphylaxis are the resulst of the rapid adsorption and/or metabolism of SP. The addition of exogenous peptidases such as pronase, chymotrypsin and an extract of black widow spider venom gland dramatically increased the rate of degradation of SP, shortened the fading response and blocked the development of tachyphylaxis. Tetrodotoxin and atropine reduced the fading time by 25%, while eserine increased its duration several-fold; these findings are consistent with the existence of a cholinergic nerve component in the mediation of some of the effects of SP. These studies demontrate that fading of the contractile effects of SP is a complex phenomenon due to desensitization of the SP receptor and, in part, to adsorption and metabolism of the peptide. The magnitude of the tachyphylaxis to SP was proportional to the concentration of the desensitizing dose of the peptide and was specific to SP and to the related peptide physalaemin; no cross-tachyphylaxis towards other agents was found.

Original languageEnglish (US)
Pages (from-to)21-34
Number of pages14
JournalEuropean Journal of Pharmacology
Volume81
Issue number1
DOIs
StatePublished - Jun 16 1982
Externally publishedYes

Fingerprint

Tachyphylaxis
Substance P
Ileum
Guinea Pigs
Peptides
Adsorption
Physalaemin
Neurokinin-1 Receptors
Pronase
Physostigmine
Tetrodotoxin
Chymotrypsin
Atropine
Cholinergic Agents
Histamine
Acetylcholine
Smooth Muscle
Peptide Hydrolases

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum. / Pablo Huidobro-Toro, J.; Chelala, César A.; Bahouth, Suleiman; Nodar, Robert; Musacchio, JoséM M.

In: European Journal of Pharmacology, Vol. 81, No. 1, 16.06.1982, p. 21-34.

Research output: Contribution to journalArticle

Pablo Huidobro-Toro, J. ; Chelala, César A. ; Bahouth, Suleiman ; Nodar, Robert ; Musacchio, JoséM M. / Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum. In: European Journal of Pharmacology. 1982 ; Vol. 81, No. 1. pp. 21-34.
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abstract = "Substance P (SP) caused an immediate and vigorous contraction of the longitudinal smooth muscle layer of the guinea-pig ileum. The contractile response to SP, unlike that to acetylcholine or histamine was not maintained but faded to baseline levels in about 6 min. When 0.3-1.0 nM SP was added the fading time was shorter than 6 min and tachyphylaxis did not develop. Higher concentrations of SP produced fading times of about 6 min that could not be increased even by adding extremely high concentrations of the peptide, up to 1 800 nM. Short fading timesand the lack of development of tachyphylaxis are the resulst of the rapid adsorption and/or metabolism of SP. The addition of exogenous peptidases such as pronase, chymotrypsin and an extract of black widow spider venom gland dramatically increased the rate of degradation of SP, shortened the fading response and blocked the development of tachyphylaxis. Tetrodotoxin and atropine reduced the fading time by 25{\%}, while eserine increased its duration several-fold; these findings are consistent with the existence of a cholinergic nerve component in the mediation of some of the effects of SP. These studies demontrate that fading of the contractile effects of SP is a complex phenomenon due to desensitization of the SP receptor and, in part, to adsorption and metabolism of the peptide. The magnitude of the tachyphylaxis to SP was proportional to the concentration of the desensitizing dose of the peptide and was specific to SP and to the related peptide physalaemin; no cross-tachyphylaxis towards other agents was found.",
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