Regulation of Muscle Differentiation: Stimulation of Myoblast Fusion in Vitro by Catecholamines

Abstract

Epinephrine and isoproterenol provoke primary chick myoblasts to initiate precocious cell fusion. Both the rise in intracellular adenosine 3' ,5-monophosphate (cyclic AMP) and cell fusion generated by these effectors are prevented by propranolol, which is a specific blocker of the beta-adrenergic receptor. Propranolol has no effect either on the precocious cell fusion provoked by prostaglandin E or on cell fusion in control cultures. The results support the idea that a rise in cyclic AMP is the critical intracellular change responsible for initiating events that culminate in myoblast differentiation 4 to 5 hours later. They also indicate that the culminate in myoblast differentiation 4 to 5 hours later. They also indicate that the hormone responsible for the positive regulation of myoblast differentiation in vitro is not acting through the beta-adrenergic receptor.

Expression of the Gs protein alpha-subunit disrupts the normal program of differentiation in cultured murine myogenic cells.

“…Although forskolin and dibutyryl cAMP, acting downstream of G s␣ in the cAMP signaling pathway, have been shown to inhibit differentiation and the expression of muscle-specific genes in the nonfusing murine muscle cell line BC 3 H1 (31), their effect on differentiation in primary and other established skeletal myoblast lines has been far less consistent (31,36,(39)(40)(41)(42)(43)(44). Agents that increase intracellular cAMP have been reported to provoke precocious fusion in some instances (40), and to inhibit myoblast fusion in others (41). In particular, reports of the effects of cAMP on myogenic differentiation in C 2 C 12 cells are highly variable.…”

cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

“…Early work implicated cAMP signaling in myogenesis, as AC activity, cAMP, and PKA activity all increase at specific times during embryonic muscle development and differentiation of myoblasts in culture (137,153,189,238,250,251). Moreover, transient treatment with catecholamines (48) or prostaglandin E 1 (249), which stimulate intracellular cAMP production, enhances fusion of primary chick myoblasts. However, this increase in cAMP production must be tightly regulated.…”

“…They then proliferate, migrate, and fuse with existing myofibers and with each other to restore normal muscle structure and function. cAMP signaling participates in muscle precursor cell differentiation (39), migration (80), and fusion (48,249). All of these cellular events are required for efficient regeneration of adult skeletal muscle (93).…”

The differentiation of avian skeletal muscle in culture: Changes in responsiveness of adenylyl cyclase to prostaglandin E1 and adrenergic agonists

“…In embryonic skeletal muscle, a transient rise in intracellular cyclic AMP is observed 4-5 hr before the onset of myoblast fusion. We have proposed that the cyclic nucleotide is a regulator of the expression of this tissue's terminally differentiated state (Zalin and Montague, 1974;Curtis and Zalin, 1982).…”