Hypothermia augments non-cholinergic neuronal bronchoconstrktion in pithed guinea-pigs

Rechtman, M. P.; King, Roger G; Boura, A. L. A.

doi:10.1016/0014-2999(91)90324-j

European Journal of Pharmacology

1991

DOI: 10.1016/0014-2999(91)90324-j

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Hypothermia augments non-cholinergic neuronal bronchoconstrktion in pithed guinea-pigs

M. P. Rechtman¹,

Roger G King²,

A. L. A. Boura³

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1992

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Cited by 2 publications

References 22 publications

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Sensory Nerves in the Airways as a Target for Drug Development

Rechtman

1992

Clin Exp Pharma Physio

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1. Electrical stimulation (2.5-10 Hz, 80 V, 1 ms for 15 s) within the spinal canal of the pithed guinea-pig pretreated with atropine, D-tubocurarine and pentolinium caused a bronchoconstrictor response, indicated by a rise of insufflation pressure. 2. The magnitude of these non-cholinergic neuronal bronchoconstrictor responses were frequency-dependent, capsaicin-sensitive and temperature-dependent. 3. Responses could be inhibited by the alpha 2-adrenoceptor agonist B-HT920 (3 mg/kg, i.v.) and the mu-opioid agonist H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA; 1 mg/kg, i.v.) and the attenuation observed could be overcome by use of the respective antagonists idazoxan (3 mg/kg, i.v.) and naloxone (3 mg/kg, i.v.). 4. Substance P-induced bronchoconstriction (0.3 micrograms/kg, i.v.), but not that due to electrical stimulation, was attenuated by indomethacin (3 mg/kg, i.v.), indicating an indirect action of substance P via a product of arachidonic acid metabolism. 5. The prostanoid product of the substance P response was probably thromboxane A2. 6. Hence, novel drug development could be directed towards tachykinin receptors or to the synthesis, release and degradation of neuropeptides.

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Sensory Nerves in the Airways as a Target for Drug Development

Rechtman

1992

Clin Exp Pharma Physio

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Tachykinin Receptors Mediating Non‐cholinergic Contraction of the Guinea‐pig Isolated Main Bronchus in Response to Field Stimulation

Heavey

Lau

Pennefather

1997

Clin Exp Pharma Physio

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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 NK1 and NK2 receptor-selective antagonists SR 140333 and SR 48968, respectively. 2. Log concentration-response curves to substance P (SP), the NK1 receptor-selective agonist [Sar9, Met(O2)11]-SP and the NK2 receptor-selective agonist [Nle10]-neurokinin (NK) A(4-10) were constructed in the presence of indomethacin (2 mumol/L) and phosphoramidon (5 mumol/L). Substance P was the least potent of these agonists. 3. In left and right main bronchi, SR 140333 (100 nmol/L) antagonized concentration-related contractions evoked by SP yielding pKB values of 8.02 and 7.68, respectively. SR 140333 (10 nmol/L) antagonized the effects of [Sar9, Met(O2)11]-SP on the left bronchus with a pKB value of 8.04. 4. SR 48968 (100 nmol/L) antagonized the effects of SP yielding pKB estimates of 7.88 (left bronchus) and 7.31 (right bronchus). 5. [Nle10]-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 [Nle10]-NKA(4-10) on the left bronchus with pKB estimates of 8.26-10.25. 6. In the presence of indomethacin (2 mumol/L), phosphoramidon (5 mumol/L) and atropine (1 mumol/L), electrical field stimulation (EFS; 30 V, 1 ms, 15 s at 1, 3, 10 and 30 Hz) produced prolonged contractions. SR 48968 (0.1 mumol/L) markedly reduced responses to stimulation, whereas SR 140333 (0.3 mumol/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 NK1 and NK2 receptor subtypes are present in the guinea-pig main bronchi with the left bronchus being more sensitive to an NK2 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.

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Hypothermia augments non-cholinergic neuronal bronchoconstrktion in pithed guinea-pigs

Cited by 2 publications

References 22 publications

Sensory Nerves in the Airways as a Target for Drug Development

Sensory Nerves in the Airways as a Target for Drug Development

Tachykinin Receptors Mediating Non‐cholinergic Contraction of the Guinea‐pig Isolated Main Bronchus in Response to Field Stimulation

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