In vivo role of the adenosine A3 receptor: N6-2-(4-aminophenyl)ethyladenosine induces bronchospasm in BDE rats by a neurally mediated mechanism involving cells resembling mast cells.
Activation of the adenosine A3 receptor subtype by the agonist N6-2-(4-aminophenyl)ethyladenosine is shown here to induce bronchospasm (increased pulmonary resistance and decreased pulmonary compliance) in BDE strain rats. The effect is substantially reduced by pretreating the rats with compound 48/80, disodium cromoglycate (30 micrograms/kg) or epinastine (10 micrograms/kg), which is compatible with involvement of mast cells. It is also substantially reduced by combined vagotomy and atropinization or by pretreatment with the NK2 receptor antagonist L-659,877, suggesting involvement of neuropeptide-mediated neural pathways. The mechanism by which activation of the adenosine A3 receptor induces bronchospasm is distinct from the mechanism by which activation of the adenosine A1 receptor induces bronchospasm. In particular, the A1 agonist 2-chloro-N6-cyclopentyladenosine can increase pulmonary resistance independently of mast cell activation. These results are in accord with the concept that a pathway exists in vivo by which activation of mast-like cells can activate axon reflexes, that adenosine acting through its A3 receptor can potentially up-regulate this pathway and that antiallergic substances such as disodium cromoglycate and epinastine may interfere with this pathway.
Meade
C J
CJ
Department of Biological Research, Boehringer Ingelheim KG, Germany.
Mierau
J
J
Leon
I
I
Ensinger
H A
HA
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001986:Bronchial Spasm / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D009479:Neuropeptides / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014628:Vagotomy; D014970:Xanthines / Q000494:pharmacology
C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D009479:Neuropeptides; D010456:Peptides, Cyclic; D058906:Purinergic P1 Receptor Agonists; D018041:Receptors, Neurokinin-2; D018047:Receptors, Purinergic P1; D014970:Xanthines; C056346:BW A1433; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); D001285:Atropine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine