"We didn't anticipate finding bone growth because we thought that once the G-protein coupled pathway was blocked, that bone formation would also be blocked," Gesty-Palmer said. "It is commonly believed that the bone-forming actions of the parathyroid hormone receptor are mediated exclusively through G-protein activation."
"I think we will find that the beta-arrestin pathways play very important roles in the body," Lefkowitz said. "It is scientific convention that the G-protein dependent signaling pathways are the best pharmaceutical targets, but as we are learning more, we see that beta-arrestin dependent pathways also have an impact on physiological processes. Getting others to accept this, however, has been like turning around a battleship it happens very slowly."
"We keep refining the science," Lefkowitz said. "With this in vivo study, we have reached the next level of specificity. With what we have learned, we may begin to create the keys to unlock targeted groups of receptors with this higher level of specificity."
With this refinement, the researchers also may achieve the control needed to avoid certain drug side effects, Lefkowitz said. "We think the next generation of drugs, in this instance for osteoporosis, will behave more as we would like them to."
Dr. Lefkowitz has taken to calling the GPCRs, which he discovered, the 7-transmembrane receptors. This name reflects the characteristic structure of the receptor proteins which weave across the cell membrane seven times, and accommodates the fact that beta-arrestin pathways may also be activated by these receptors.
|Contact: Mary Jane Gore|
Duke University Medical Center