Interactions of full and partial agonists with beta-adrenergic receptors on intact L6 muscle cells.
A nonfusing variant of L6 muscle cells was used to study the interactions of 16 agonists and 8 antagonists with beta-adrenergic receptors. Membranes prepared from L6 cells and intact cells in monolayer culture were used. Beta-adrenergic receptors on broken cells and on intact cells had the same affinities for all of the antagonists studied. Studies of the inhibition of the binding of [125I]iodohydroxybenzylpindolol by agonists indicated that two states of the receptor can exist on intact cells attached to the substratum. The form of the receptor normally present on intact cells appeared to have the same properties as receptors on membranes when assayed in the presence of GTP. Several full agonists converted this form of the receptor to a form which had a 40- to 50-fold lower affinity for agonists. This conversion appeared to occur during the first few minutes of exposure to an agonist. Four of the agonists tested did not convert any of the receptors on intact cells to a form with a low affinity for agonists. Included in this group of agents were two full agonists and two partial agonists. Therefore, interactions of these drugs with receptors on broken or intact cells were the same. Several other full and partial agonists converted some of the receptors on intact cells to a low-affinity form, and their interactions with receptors on intact cells were characterized by shallow inhibition curves. The conversion of beta-adrenergic receptors on intact cells to a low-affinity state did not appear to be a prerequisite for the decrease in the rate of agonist-stimulated cyclic AMP accumulation that occurs 1-2 min after exposure of L6 cells to agonists. Studies were also carried out on viable intact cells detached from plates following brief exposure to trypsin or EDTA. The properties of receptors on suspended cells were the same as those of receptors on broken cells when assayed in the presence of GTP, rather than being similar to the properties of receptors on attached cells. In summary, data are presented indicating that agonists with the same potency and intrinsic activity in membrane preparations (and intact cells in suspension) can interact very differently with beta-adrenergic receptors on intact cells attached to the substratum. Thus, certain agonists cause a rapid conversion of beta-adrenergic receptors to a form which has a low affinity for agonists. This effect is seen with some but not all agonists and is seen only in studies with attached cells.
D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009132:Muscles; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C011878:iodohydroxybenzylpindolol; C002904:zinterol; D010869:Pindolol; D000242:Cyclic AMP; D007545:Isoproterenol; C100251:salmefamol