Beta-adrenoceptor desensitization induced by antigen challenge in guinea-pig trachea.
As beta-adrenoceptor function in the lung could be relevant in asthma, we carried out a functional and biochemical study of the possible occurrence of beta-receptor desensitization after the anaphylactic reaction induced in vitro in actively sensitized guinea-pig tracheas. The relaxing effect of epinephrine and vasoactive intestinal polypeptide (VIP) was tested in tracheal strips. Binding was studied with tracheal membranes and 125I-cyanopindolol. Antigen challenge resulted in a marked decrease of epinephrine-induced relaxation paralleled by a 50% reduction in beta-receptor number. The adrenergic system was specifically affected since VIP-induced relaxation was not modified by the anaphylactic reaction. In some experiments tissues were pretreated with hydrocortisone or indomethacin. Both these drugs prevented antigen exposure from impairing epinephrine relaxation, suggesting the involvement of eicosanoids in this phenomenon. Our data clearly indicate the occurrence of beta-receptor desensitization as a consequence of the anaphylactic reaction, thus impairment of the adrenergic system might play a role in asthma.
Daffonchio
L
L
Institute of Pharmacological Sciences, University of Milan, Italy.
Abbracchio
M P
MP
Di Luca
M
M
Hernandez
A
A
Amadeo
L
L
Cattabeni
F
F
Omini
C
C
D000818:Animals; D000941:Antigens / Q000276:immunology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015777:Eicosanoids / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000941:Antigens; D001095:Arachidonic Acids; D015777:Eicosanoids; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D016718:Arachidonic Acid; D014660:Vasoactive Intestinal Peptide; D020120:Iodocyanopindolol; D010869:Pindolol; D006854:Hydrocortisone; D007213:Indomethacin; D004837:Epinephrine