Norepinephrine-induced calcium signaling and expression of adrenoceptors in avian tendon cells

Abstract

Sympathetic efferent nerves are present in tendons, but their function within tendon is unknown. alpha(1)-Adrenoceptors are expressed by a variety of cell types. In the presence of norepinephrine (NE), adrenoceptors activate G(q/11) signaling pathways that subsequently increase intracellular Ca(2+) concentration ([Ca(2+)](ic)). It was hypothesized that avian tendon cells express functional adrenoceptors that respond to NE by increasing [Ca(2+)](ic). Avian tendon cells were analyzed for mRNA expression of alpha(1)-adrenoceptors by RT-PCR. Avian tendons expressed the alpha(1A)- and alpha(1B)-adrenoceptor subtypes. Furthermore, both tendon surface epitenon cells and internal fibroblasts infused with a Ca(2+)-sensitive dye, fura 2, and stimulated with NE responded by increasing [Ca(2+)](ic). KMD-3213, an alpha(1A)-adrenoceptor antagonist, significantly reduced the Ca(2+) response. Other adrenoceptor antagonists had no effect on the Ca(2+) response. The absence of extracellular Ca(2+) also significantly reduced the response to NE, indicating that Ca(2+) influx contributed to the rise in [Ca(2+)](ic). This study provides the first evidence that tendon cells express adrenoceptors and that the NE-induced Ca(2+) response is coupled to the alpha(1A)-adrenoceptor subtype.

Neuropeptides in tendinopathy

“…Additionally, these same tenocytes demonstrate immunoreactions for alpha-adrenergic receptors (11). Similar findings have been reported for avian flexor tenocytes, which demonstrated mRNA expression of alpha-adrenergic receptors (47). Stimulation of avian tenocyte cultures with noradrenaline resulted in a wave of calcium signaling within tenocytes (47).…”

“…Similar findings have been reported for avian flexor tenocytes, which demonstrated mRNA expression of alpha-adrenergic receptors (47). Stimulation of avian tenocyte cultures with noradrenaline resulted in a wave of calcium signaling within tenocytes (47). It is therefore possible that noradrenaline may lead to downstream responses such as tenocyte proliferation and/or modulation of extracellular matrix production.…”

Mechanobiology of tendon

“…The activation of these channels permit calcium (Ca 2+ ) and other ions (e.g., sodium and potassium) to influx followed by membrane depolarization (Sackin, 1995). Norepinephrine treatment of avian tendon cells increased the expression of functional adrenoceptors by increasing intracellular Ca 2+ concentration (Wall et al, 2004). Cyclic stretching stimulated Ca 2+ influx into osteoblastic cells (Vadiakas and Banes, 1992), and laminar fluid flow increased intracellular Ca 2+ in human disc cells (Elfervig et al, 2001).…”

Activation of α1A-adrenergic receptor promotes differentiation of rat-1 fibroblasts to a smooth muscle-like phenotype

“…However, a recent study showed the expression of a functional α 1A -AR in primary tendon fibroblasts [11]. In rat-1 cells, a transformed cell line from embryonic fibroblast, expressing different subtypes of α 1 -AR, phenylephrine (PE), an α 1 -AR agonist, activates phospholipase D and releases arachidonic acid [12].…”