Paccar

PACCAR Inc. is a Fortune 500 company and counts among the largest manufacturers of medium- and heavy-duty trucks in the world, and has substantial manufacturing in light and medium vehicles through its various subsidiaries. For its leadership in the development of aerodynamic, lightweight commercial vehicles that has led to reduced fuel consumption and increased efficiencies, PACCAR, Inc was awarded the National Medal of Technology at the White House in 2006. The company’s presence has been especially strong in Renton, Washington, where it remains the oldest continually operating business. PACCAR's assembly plant in Renton was recognized as one of the best workplaces for commuters for the fifth consecutive year by the National Center for Transit Research in June 2013. The plant also celebrated its 20th anniversary in June 2013 and has produced more than 130,000 heavy-duty and medium-duty Kenworth trucks since it started its operations in 1993.

History

Calcium-sensing receptor

The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).

Signal transduction

The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Increased calcium binding on the extracellular side gives a conformational change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway, presumably through a G_qα type of G protein, which ultimately increases intracellular concentration of calcium, which inhibits vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some sources state) the cAMP dependent pathway.

Pathology

Mutations that inactivate a CaSR gene cause familial hypocalciuric hypercalcemia (FHH) (also known as familial benign hypercalcemia because it is generally asymptomatic and does not require treatment), when present in heterozygotes. Patients who are homozygous for CaSR inactivating mutations have more severe hypercalcemia. Other mutations that activate CaSR are the cause of autosomal dominant hypocalcemia or Type 5 Bartter syndrome. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.