Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo.
OBJECTIVE
To investigate the effects of adenosine receptor agonists and antagonists on 5-HT release from rat isolated pleural mast cells and on plasma protein extravasation in the skin of conscious rats. In vitro


METHODS
Rat isolated pleural mast cells were loaded with [14C] 5-HT, sensitised with mouse monoclonal anti-DNP and then challenged with human serum albumin-DNP. DNP-stimulated 5-HT release from mast cells was determined. In vivo


METHODS
Rats, loaded intravenously with [125I] human serum albumin, were injected intradermally with adenosine agonists at sites on the back. 30 min later plasma protein extravasation at each injection site was determined.


RESULTS
In isolated mast cells, each adenosine agonist enhanced DNP-induced 5-HT release, N6-(3-iodobenzyl)-5-(N-methyl-carboxamidoadenosine), (IB-MECA), being the most potent agonist. The adenosine A1/A2 antagonist, 8-phenyltheophylline (8-PT), had no effect on the response to IB-MECA. In contrast, 3-(4-amino-iodobenzyl)-8-[4-[[[carboxy]methyl]oxy]phenyl]-1-propylxanthi ne, (I-ABOPX), inhibited (pA2 6.2) the IB-MECA responses. In the skin of conscious rats, intradermal IB-MECA produced a marked plasma protein extravasation (PPE) which was mimicked by N6-2-(4-aminophenyl)-ethyladenosine (APNEA). The PPE produced by IB-MECA was not affected by either 8-PT or CGS15943A, but was virtually abolished by cyproheptadine and in rats pre-treated with Compound 48/80.


CONCLUSIONS
These results indicate that stimulation of adenosine A3 receptors both enhances degranulation in vitro and directly produces degranulation of rat mast cells in vivo.
Reeves
J J
JJ
Receptor Pharmacology Unit, Glaxo Wellcome Research & Development Ltd., Stevenage, Hertfordshire, UK.
Jones
C A
CA
Sheehan
M J
MJ
Vardey
C J
CJ
Whelan
C J
CJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology*; D003533:Cyproheptadine / Q000494:pharmacology; D004140:Dinitrophenols / Q000633:toxicity; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010994:Pleura / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012709:Serum Albumin / Q000008:administration & dosage / Q000633:toxicity; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001798:Blood Proteins; D004140:Dinitrophenols; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D018047:Receptors, Purinergic P1; D012702:Serotonin Antagonists; D012709:Serum Albumin; D014230:Triazoles; D014970:Xanthines; C086749:BW A522; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D003533:Cyproheptadine; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine