ß‐Adrenergic Receptor Activation Increases Acetylcholine Receptor Number in Cultured Skeletal Muscle Myotubes

Abstract

Treatment of embryonic chick muscle myotubes with the beta-adrenergic agonist isoproterenol increased the number of surface membrane nicotinic cholinergic receptors. Receptor degradation was unaffected by isoproterenol, suggesting that receptor synthesis was increased. The effect of isoproterenol appears to be mediated by the beta-adrenergic receptor adenylate cyclase system for the following reasons: (a) The response to isoproterenol was dose-dependent and stereospecific. (b) The response to catecholamines followed the order isoproterenol greater than epinephrine greater than norepinephrine. (c) Alprenolol, a beta-adrenergic antagonist, but not phentolamine, an alpha-antagonist, abolished the effect. (d) The maximal effects of isoproterenol and cholera toxin, an activator of adenylate cyclase, were not additive. These results suggest that under certain physiological states catecholamines may play an important role in the regulation of cholinergic receptors.

Octopamine enhances neuromuscular transmission in developing and adult moths, Manduca sexta

“…Currently, there is no direct evidence that monoamines are necessary for the development of neuromuscular junctions mediated by glutamate in insects or by acetylcholine in vertebrates. Support for this possibility is provided by the observation that treatment of chick myotubes with the 0-adrenergic agonist isoproterenol increases the number of cholinergic receptors (Blosser, 1983). In addition, monoamines appear to be important for the development and stabilization of some synapses in the vertebrates CNS (Kasamatsu, 1983).…”

Cholinergic properties of desipramine and amoxapine: Assessment using a thermoregulation paradigm

“…Nomura et al (1982a), for example, reported that isoproterenol induced cholinergic system supersensitivity and up-regulation of QNB binding sites in rat myocardium. Blosser (1983) found that activation of B-adrenergic receptors increased the density of cholinoceptors in chick myotubes. These reports are consistent with the capacity of norepinephrine (Beani et al, 1978) to inhibit the release of acetylcholine from brain slices.…”

“…The second category of agents producing up-regulation and supersensitivity of muscarinic cholinergic systems is comprised of at least five classes of agents which act at the presynaptic nerve terminal to inhibit the release of acetylcholine (Dilsaver, in press). Opiate agonists (Domino and Wilson, 1973;Jhamandas et al, 1973a,b), cannabinoids (Kumbarachi and Nastuk, 1980;Layman and Milton, 1971;Yoshimura et al, 1974), barbiturates (Nordberg and Wahlstrom, 1981;Nordberg and Sundwall, 1977;Wahlstrom and Nordberg, 1979;Wahlstrom and Ekwall, 1976;Wahlstrom, 1978)) ethanol (Rabin et al, 1980;Smith, 1983;Tabakoff et al, 1979), and certain serotinergic (ijgren et al, 1985a,b), dopaminergic (Ehlert et al, 1981) and adrenergic (Blosser, 1983) agonists are in this class. Nomura et al (1982a), for example, reported that isoproterenol induced cholinergic system supersensitivity and up-regulation of QNB binding sites in rat myocardium.…”

Epinephrine, the neglected catecholamine

“…The notion that beta stimulation can affect other types of receptors is testable in that it leads to the prediction that propranolol should antagonize the alpha-1 sensitizing actions of chronic antidepressants. Furthermore the notion is not that farfetched since it has been found that chronic stimulation of beta adrenergic receptors in cultured muscle cells with ISO (isoproterenol) or in adult rat heart in vivo with DMI leads to an increased density of non-beta adrenergic receptors, Response/Stone: Catecholamines and antidepressant therapy that is, nicotinic and muscarinic cholinergic receptors (Blosser 1983;Nomura, Kajiyama & Oki 1982). Not all investigators have found these effects for DMI, however (Hess, Prostran, Carricato, Locke, Brzozowski, Sills & Viscusi 1982).…”