Novel α 1 ‐adrenergic receptor signaling pathways: Secreted factors and extracellular matrix regulate cell adhesion, motility and transcription

α 1 ‐adrenergic receptor (α 1 ‐ARs) subtypes (α 1A , α 1B and α 1D ) regulate multiple signal pathways such as PLC, PKC, and MAPKs. We employed microarray technology to explore the effects of both short (1h) and long‐term (18h) activation of the α 1A ‐AR to enable RNA changes to occur downstream of earlier well‐characterized signaling pathways, promoting novel couplings. PCR studies confirmed that PKC was a critical regulator of gene expression with secreted growth factors (IL‐6, FGF7) also contributing to expression alterations. We next focused on two novel pathways that may be mediated through α 1A ‐AR stimulation, due to the clustering of gene expression changes for cell adhesion/motility (syndecan‐4 and tenascin‐C) and hyaluronan (HA) signaling. We confirmed that α 1 ‐ARs mediated vitronectin‐dependent cell adhesion in three cell types that was also integrin and FGF7‐dependent. α 1 ‐AR activation also inhibited cell migration, which was substrate‐independent suggesting regulation of cell motility. α 1 ‐AR activation also increased the expression and deposition of HA, a glycosaminoglycan, which displayed two distinct structures: pericellular coats and long cable structures, as well as increasing expression of the HA receptor, CD44. Since long cable structures of HA can bind leukocytes, this suggests that α 1 ‐ARs may be involved in pro‐inflammatory responses. Our results indicate α 1 ‐ARs interact with the extracellular matrix to regulate cell adhesion, motility and pro‐inflammatory responses through novel signaling pathways.