Corticotropin releasing hormone-induced potentiation of substance p-mediated contraction of guinea pig airway smooth muscle

M. A. McAlexander, B. J. Undem

Research output: Contribution to journalArticlepeer-review

Abstract

Corticotropin releasing hormone (CRH) is known to have antiinflammatory actions via the endocrine system. CRH may also serve as a local modulator of inflammation within tissues (Pharm. Rev. 43:425, 1991). In airways, CRH has been shown to acutely inhibit neurogenic tachykim'n-mediated plasma extravasation (Eur. J. Pharm. 140:63, 1987), suggesting that CRH may cause inhibition of tachykinin release from airway afferent fibers. We examined the effect of CRH on the tachykinergic contractions of the guinea pig isolated airway. Exposing the isolated guinea pig left bronchus to 1 |ig/ml CRH significantly enhanced the tachykininmediated smooth muscle contraction elicited by electrical field stimulation (8 Hz, 20V,10s) from 17.7±2.2% to 29.5±3.7% of maximum (n=8; p<0.01). CRH had a similar effect on contractions elicited by bath-applied capsaicin (n=8; p<0.01). To characterize the effect of CRH as pre- or postjunctional, concentration-response curves to substance P (SP) and neurokinin A (NKA) were performed. CRH significantly shifted the SP curve leftward. The negative log (M) ECso for SP was 7.4±0.2 in the absence of CRH and 8.1±0.3 in the presence of CRH (l (ig/ml; n=8; p<0.01). This effect of CRH on SP persisted in the presence of the peptidase inhibitor thiorphan (3 μM; n=6). The NKA concentration-response curve for airway contraction was unaffected by CRH (n=6). These data indicate CRH can enhance airway smooth muscle response to tachykinergic nerve stimulation. This effect may be due to an enhancement of the muscle response to SP.

Original languageEnglish (US)
Pages (from-to)A162
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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