The Beta2 Adrenergic Receptor

How the Beta2 Adrenergic Receptor Works
The beta2 adrenergic receptor is stimulated by adrenalin, which results in the activation of an enzyme called adenylyl cyclase (AC), which in turn leads to increased formation of a cell signaling molecule called cyclic AMP (cAMP). This signaling process is very important to gene expression during fetal development and could be significantly affected by over stimulation of the beta2 adrenergic receptor. During fetal life, the beta2 adrenergic receptor has the potential to be over stimulated because it does not turn off signaling very well. This characteristic may create vulnerability to environmental influences that act on the beta2 adrenergic receptor, especially when the more active versions of this receptor are present.

For example, an environmental factor may be stress experienced by the mother or a medication taken by her. An environmental influence that has been shown to act on the beta2 adrenergic receptor is a drug called terbutaline, which can be given to a pregnant woman to arrest preterm labor. Terbutaline stimulates the beta2 adrenergic receptors in the mother, which in turn stimulates cell signaling in the smooth muscle cells of the uterus. This relaxes the uterine wall and slows or stops the early contractions. But, terbutaline also crosses the placenta and has the potential to act on all the beta2 adrenergic receptors in the tissues of the fetus, including the developing brain. In the mother, continued exposure to terbutaline eventually turns off the beta2 adrenergic receptor signaling because the mother’s cell receptors are mature. In the fetus, continued exposure to terbutaline can cause the beta2 adrenergic receptor to constantly signal, which can interfere with crucial aspects of fetal development. This scenario may be more pronounced when the more active versions of the receptor are present. The over stimulation of the beta2 adrenergic receptor, which ultimately increases cyclic AMP production, has the potential to affect hundreds of crucial chemical pathways in fetal development as well as gene activation.

In a recent study, when terbutaline was given to rats at an age equivalent to the second trimester of human pregnancy, the offspring developed changes in the brain that are analogous with those described in autism. Other rat studies have shown that when the beta2 adrenergic receptor is over stimulated in a fetus, during critical periods in development, the fetus is also at increased risk for functional brain abnormalities after birth, when exposed to environmental factors, such as pesticides. The findings in the rat studies are significant alone, and may be profound when considering the fact that a human fetus can possess a more active version of the beta2 adrenergic receptor, providing for an even more significant and abnormal outcome.

The beta2 adrenergic receptor has an early and ongoing organizing role in fetal cell development, which directly influences later functional development in a human being. The altered programming of the beta2 adrenergic receptor that results after fetal over-stimulation may also act as an epigenetic influence because the expression of many genes depends upon the cell signaling provided by the beta2 adrenergic receptor. Animal studies have shown that over stimulation of the beta2 adrenergic receptor during fetal life results in increased or decreased cell signaling from the enzyme, adenylyl cyclase, compared to control animals, which results in variable changes in the brain and other organs. The degree, characteristics and onset of the changes depend on the region of the brain that is studied, and the age at which it is investigated. Because many genes are activated by signaling through adenylyl cyclase by way of cyclic AMP, fetal over stimulation of the beta2 adrenergic receptor and the adenylyl cyclase signaling resulting from it can act as an epigenetic influence on gene expression during later development.

The beta2 adrenergic receptor and molecules involved in its signaling, as well as other cell receptors, are important in fetal brain development, needs further study as we begin to focus on future scientific research.