Beta 2-adrenergic receptors on eosinophils. Binding and functional studies.
We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed.
Yukawa
T
T
Department of Thoracic Medicine, National Heart and Lung Institute, Brompton Hospital, London, United Kingdom.
Ukena
D
D
Kroegel
C
C
Chanez
P
P
Dent
G
G
Chung
K F
KF
Barnes
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004802:Eosinophilia / Q000473:pathology; D004804:Eosinophils / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D010869:Pindolol / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000420:Albuterol