Endogenous noradrenaline masks beta-adrenergic receptors in rat heart membranes via tight agonist binding.
The tight binding of noradrenaline (NA) to beta-adrenergic receptors was studied in membranes from the left ventricular myocardium of the rat. Addition of GTP (0.1 mM) to membrane preparations from control rats (NA concentration 8.5 +/- 2.1 nM) caused a 4-35% (N = 8) increase (P less than 0.01) in the number of specific binding sites of [125I](-)pindolol. In contrast, addition of GTP did not cause any changes in the number of beta-adrenergic receptors in heart membranes from reserpinized animals (NA concentration less than 0.1 nM). In heart membranes from reserpinized animals, preincubation with NA (followed by washing) revealed a time- and concentration-dependent decrease with a maximum of 35-40% in the [125I](-)pindolol-binding sites. This agonist-mediated decrease in the number of receptors was prevented if GTP was also present in the NA-preincubation medium. It is concluded that NA can undergo tight binding to beta-adrenergic receptors in rat heart membranes. The heart-membrane preparations contain endogenous NA which, via tight agonist binding, is responsible for masking part of the beta-adrenergic receptor population.
Nerme
V
V
Severne
Y
Y
Abrahamsson
T
T
Vauquelin
G
G
D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000032:analysis; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000032:analysis* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; C029247:3-iodopindolol; D006160:Guanosine Triphosphate; D012110:Reserpine; D010869:Pindolol; D009638:Norepinephrine