The effects of halothane on the human beta-adrenergic receptor of lymphocyte membranes.
The effects of halothane on beta-adrenergic receptor antagonist interaction were studied using the membranes of human lymphocytes as a model. Membrane preparations of lymphocytes were obtained from blood samples withdrawn from seven healthy young volunteers. Beta-receptor studies were performed using (-)125I iodocyanopindolol (125ICP) binding. Non-specific binding was determined in the presence of (-)isoproterenol. Beta-receptor density (Bmax) and the dissociation constant (KD) for 125ICP were determined from saturation curves. Beta-receptor affinity for agonists evaluated by the IC50 (the concentration of isoproterenol required to inhibit 50% of specific 125ICP binding) and the dissociation constant (KL) for isoproterenol was established from competition curves. The effect of halothane 1%, in an air oxygen mixture (oxygen fraction: 0.3) administered by tonometry during ligand membrane incubation, on beta-adrenergic receptor, was compared to that of control experiments not exposed to halothane. Halothane produced a moderate but significant decrease of Bmax (-10%) and a significant increase in non-specific binding (+30%), while KD, IC50, and KL were unchanged. The authors conclude that halothane, in vitro, decreases beta-adrenergic receptor density. This effect could be mediated by an alteration of the receptor in the membrane due to action of halothane on the lipid phase of the membrane.
Marty
J
J
Département d'Anesthésie-Réanimation, Hôpital Bichat, Paris, France.
Nivoche
Y
Y
Nimier
M
M
Rocchiccioli
C
C
Luscombe
F
F
Henzel
D
D
Loiseau
A
A
Desmonts
J M
JM
D000328:Adult; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D006221:Halothane