Adenosine A3 receptor-mediated airway microvascular leakage: role of mast cells and tachykinins.
To determine whether adenosine A3 receptor stimulation produces airway inflammation and, if so, what the mechanism of action is, we studied microvascular permeability in the rat trachea. After intravenous injection of Evans blue dye, adenosine and various adenosine analogues were given by inhalation, and the tracheal microvascular permeability was determined by a photometric measurement of extravasated dye. N6-2-(4-aminophenyl)-ethyladenosine (APNEA), an adenosine A3 receptor agonist, dose dependently increased plasma protein extravasation, whereas adenosine, the A1-receptor agonist N6-(R-phenylisopropyl)-adenosine, or the A2-receptor agonist 5'-N-ethyl-carboxamidoadenosine had no effect. The effect of APNEA was not altered by the adenosine A1/A2 receptor antagonist 8-(p-sulphophenyl)-theophylline, but was reduced by depletion of mast cell-derived mediators with compound 48/80 or pretreatment with the tachykinin NK1 receptor antagonist CP99,994. These results suggest that activation of A3 receptor specifically increase airway microvascular permeability probably via mast cell-derived mediators and tachykinins.
Nagano
Y
Y
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Japan.
Tamaoki
J
J
Nishimura
K
K
Yamawaki
I
I
Nagai
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D016084:Bronchoconstriction / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015320:Tachykinins / Q000502:physiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D010880:Piperidines; D011453:Prostaglandins; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D015320:Tachykinins; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D003189:p-Methoxy-N-methylphenethylamine; D000241:Adenosine