褐色脂肪細胞でのノルアドレナリンによるCa²⁺応答のサイロキシンによるα/β作用変換

抄録

In brown adipocytes, the β-action of noradrenaline is known to cause thermogenesis, which seems to be facilitated by the action of thyroid hormone. On the other hand, the α-action of noradrenaline causes a large increase in Ca²⁺ via intracellular Ca²⁺ release and subsequent store-operated Ca²⁺ entry, albeit its physiological function is unknown. We have studied by fluorometric Ca²⁺-imaging techniques how thyroxin modifies the actions of noradrenaline to increase intracellular Ca²⁺ in cultured rat brown adipocytes. Noradrenaline (1-10 μM) caused initially sharp and then plateaued rises in Ca²⁺, which was blocked by phentorlamine (10 μM: α-antagonist), but not by propranolol (1 μM: β-antagonist). Phenylephrine (10 μM: α-agonist) caused a rise in Ca²⁺ similar to that by noradrenaline. When rat adipocytes were pretereated with thyroxin (1-4 μM) for more than 4 min, which produced no or slight decrease in Ca²⁺, noradrenaline induced a transient rise in Ca²⁺ in short duration, which was followed by a marked, sustained reduction in Ca²⁺. This decrease in Ca²⁺ was blocked by propranolol, but not by phentolamine. Isoprenaline (1 μM: β-agonist) produced a similar decrease in Ca²⁺ under this condition, but not if no pretreatment with thyroxin was made. These results suggest that thyroxin primes the mechanism of the β-action of noradrenaline to decrease intracellular Ca²⁺ in brown adipocytes presumably via the enhancement of Ca²⁺ uptake and/or extrusion, overcoming the α-action to raise Ca²⁺. [Jpn J Physiol 54 Suppl:S75 (2004)]