Contractile responses to adenosine, R-PIA and ovalbumen in passively sensitized guinea-pig isolated airways.
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.
Martin
Timothy J
TJ
Department of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cathays Park, Cardiff, CF10 3XF, U.K.
Broadley
Kenneth J
KJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D007106:Immune Sera; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D014665:Vasodilator Agents; D016210:Methacholine Chloride; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; C047235:N-(1-methyl-2-phenylethyl)adenosine; D006632:Histamine; D010047:Ovalbumin; D000241:Adenosine