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Contractile responses to adenosine, R-PIA and ovalbumen in passively sensitized guinea-pig isolated airways

Martin, T. J. and Broadley, Kenneth John 2002. Contractile responses to adenosine, R-PIA and ovalbumen in passively sensitized guinea-pig isolated airways. British Journal of Pharmacology 137 (6) , pp. 729-738.

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Abstract

1. Responses to adenosine, R-PIA and ovalbumen were examined in guinea-pig isolated superfused tracheal spirals to determine the effects of passive sensitization by overnight incubation in serum from ovalbumen (OA)-sensitized or non-sensitized guinea-pigs. 2. Tissues incubated with serum from non-sensitized and OA-sensitized guinea-pigs contracted (0.07+/-0.02 and 0.04+/-0.01 g, respectively) to adenosine (300 micro M) whereas non-incubated or Krebs-incubated tissues produced no contractions to adenosine or ovalbumen (10 micro g). Ovalbumen caused substantial contractions (0.40+/-0.09 g) after OA-sensitized serum incubation and significantly (P<0.05) smaller contractions (0.08+/-0.03 g) after non-sensitized serum incubation. Tracheae from guinea-pigs actively sensitized to ovalbumen 14-21 days beforehand also contracted to adenosine, R-PIA (3 micro M) and ovalbumen. 3. The A(1)/A(2) adenosine receptor antagonist, 8-phenyltheophylline (8-PT, 3 micro M), failed to antagonize these contractions, suggesting that A(1)/A(2) adenosine receptors were not involved. 4. Unlike adenosine, R-PIA (3 micro M) produced contractions in non-incubated (0.23+/-0.04 g) or Krebs-incubated (0.15+/-0.04 g) tracheae, as well as after passive and active sensitization. None of these responses were blocked by 8-PT. 5. The A(3) receptor agonist, IB-MECA, in the presence of 8-PT produced small contractions in passively sensitized tracheae (10 micro M, 0.02+/-0.003 g) and, in larger doses (100 micro M and 1 mM), contracted actively sensitized tracheae. 6. In actively sensitized trachea, the A(3) receptor antagonist, MRS-1220 (100 nM), significantly (P<0.05) attenuated adenosine contractions in the presence of 8-PT from 0.23+/-0.07 g to 0.07+/-0.03 g. 7. These results show that passive, like active sensitization, reveals bronchoconstrictions to adenosine of isolated tracheae. The insensitivity to 8-PT blockade, the antagonism by MRS-1220, and the fact that the A(3) receptor agonist, IB-MECA, mimics this response, suggest involvement of A(3) receptors. R-PIA, however, has a different profile of adenosine receptor activity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Publisher: Wiley-Blackwell
ISSN: 0007-1188
Related URLs:
Last Modified: 04 Jun 2017 03:01
URI: http://orca.cf.ac.uk/id/eprint/15406

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