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TACHYKININ RECEPTORS MEDIATING NON‐CHOLINERGIC CONTRACTION OF THE GUINEA‐PIG ISOLATED MAIN BRONCHUS IN RESPONSE TO FIELD STIMULATION
Author(s) -
Heavey Melanie L.,
Lau Winnie AK,
Pennefather Jocelyn N.
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb02111.x
Subject(s) - contraction (grammar) , stimulation , guinea pig , cholinergic , tachykinin receptor , chemistry , endocrinology , receptor , medicine , substance p , neuropeptide
SUMMARY 1. The primary aim of the present study was to classify the receptors activated by tachykinins released by field stimulation of intramural nerve terminals of the guinea‐pig isolated main bronchus by using the novel non‐peptide NKi and NK 2 receptor‐selective antagonists SR140333 and SR 48968, respectively. 2. Log concentration‐response curves to substance P (SP), the NKi receptor‐selective agonist [Sar 9 , Met(O2) 11 ]‐SP and the NK 2 receptor‐selective agonist [Nle 10 ]‐neurokinin (NK) A(4‐10) were constructed in the presence of indomethacin (2 μmol/L) and phosphoramidon (5 (μmol/L). Substance P was the least potent of these agonists. 3. In left and right main bronchi, SR 140333 (lOOnmol/L) antagonized concentration‐related contractions evoked by SP yielding pK B values of 8.02 and 7.68, respectively. SR 140333 (10 nmol/L) antagonized the effects of [Sar 9 , Met(O 2 ) 11 ]‐SP on the left bronchus with a pK B value of 8.04. 4. SR 48968 (100 nmol/L) antagonized the effects of SP yielding pK B estimates of 7.88 (left bronchus) and 731 (right bronchus). 5. [Nle 10 ]‐NKA(4‐10) was more potent in the left than in the right main bronchus. SR 48968 (0.1‐10 nmol/L) antagonized the effects of [Nle I0 ]‐NKA(4‐10) on the left bronchus with pK B estimates of 8.26‐10.25. 6. In the presence of indomethacin (2 μmol/L), phosphoramidon (5 μmol/L) and atropine (1 (μmol/L), electrical field stimulation (EFS; 30 V, 1ms, 15 s at 1, 3 , 10 and 30 Hz) produced prolonged contractions. SR 48968 (0.1 μmol/L) markedly reduced responses to stimulation, whereas SR 140333 (0.3 μmol/L) caused a small but significant rightward displacement of the log frequency‐response curve. In combination, these concentrations of SR 48968 and SR 140333 produced complete inhibition to field stimulation at 10 Hz. 7. These results indicate that: (i) both NK 1 and NK 2 receptor subtypes are present in the guinea‐pig main bronchi with the left bronchus being more sensitive to an NK 2 receptor agonist; and (ii) EFS of the main bronchus leads to frequency dependent contractions due to the release of tachykinin(s) that predominantly activate an NK2 receptor.