Short term and long term effects of beta-adrenergic effectors and cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle.
The effects of short term stimulation of beta-adrenergic receptors and elevations in intracellular cyclic AMP on nitrendipine-sensitive voltage-dependent Ca2+ channels of skeletal muscle cells in vitro has been studied using both the 45Ca2+ flux technique and [3H] nitrendipine-binding experiments. Isoproterenol increased the nitrendipine-sensitive 45Ca2+ influx under depolarizing conditions. The effects of isoproterenol were additive to those of depolarization and were antagonized by alprenolol. Half-maximal inhibition of 45Ca2+ influx induced both by depolarization and by isoproterenol occurred at a nitrendipine concentration of 1 nM. Treatments that resulted in an increased level of intracellular cyclic AMP, such as treatment with 1-methyl-3-isobutylxanthine, theophylline, dibutyryl cyclic AMP, or 8-bromocyclic AMP also resulted in an increased rate of 45Ca2+ entry via nitrendipine-sensitive Ca2+ channel. In contrast, long term treatment of myotubes in culture with isoproterenol and other compounds that increased intracellular cyclic AMP led to a large increase in the number of nitrendipine receptors. This increase was accompanied by a 4-10-fold decrease in the affinity of the receptors for nitrendipine. Alprenolol inhibited the long term effects of isoproterenol. In vivo treatment of 7-day-old chicks with reserpine and alprenolol produced a decrease in the number of skeletal muscle nitrendipine receptors. This decrease in receptor number was accompanied by an increase in the affinity of nitrendipine for its receptor by a factor of 4 to 5. These effects on the nitrendipine receptor were prevented by simultaneous injection of isoproterenol. The results are discussed in relation to the role of beta-adrenergic receptors and intracellular cyclic AMP in the regulation of skeletal muscle Ca2+ channels.
A
A
Schmid
J F
JF
Renaud
M
M
Lazdunski
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009132:Muscles / Q000196:embryology / Q000502:physiology*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009568:Nitrendipine; D011978:Receptors, Nicotinic / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D007473:Ion Channels; D011978:Receptors, Nicotinic; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000526:Alprenolol; D012110:Reserpine; D009568:Nitrendipine; D013806:Theophylline; D000242:Cyclic AMP; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine