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RECEPTORS AND SIGNAL TRANSDUCTION

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

¹Department of Biomedical Engineering, ²Department of Orthopaedics, ³Department of Cell and Molecular Physiology, and ⁴Curriculum in Applied and Material Sciences, University of North Carolina at Chapel Hill, Chapel Hill 27599; and ⁵Flexcell International Corporation, Hillsborough, North Carolina 27278

Submitted 19 February 2004 ; accepted in final form 9 June 2004

Sympathetic efferent nerves are present in tendons, but their function within tendon is unknown. 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 Ca²⁺ concentration ([Ca²⁺]_ic). It was hypothesized that avian tendon cells express functional adrenoceptors that respond to NE by increasing [Ca²⁺]_ic. Avian tendon cells were analyzed for mRNA expression of ₁-adrenoceptors by RT-PCR. Avian tendons expressed the _1A- and _1B-adrenoceptor subtypes. Furthermore, both tendon surface epitenon cells and internal fibroblasts infused with a Ca²⁺-sensitive dye, fura 2, and stimulated with NE responded by increasing [Ca²⁺]_ic. KMD-3213, an _1A-adrenoceptor antagonist, significantly reduced the Ca²⁺ response. Other adrenoceptor antagonists had no effect on the Ca²⁺ response. The absence of extracellular Ca²⁺ also significantly reduced the response to NE, indicating that Ca²⁺ influx contributed to the rise in [Ca²⁺]_ic. This study provides the first evidence that tendon cells express adrenoceptors and that the NE-induced Ca²⁺ response is coupled to the _1A-adrenoceptor subtype.

-adrenoceptors; fibroblasts; catecholamines; tenocytes