Agonists at β1 receptors in the heart and β2 receptors in airway smooth muscle both stimulate GPCR (G-protein coupled receptor) signaling pathways associated with the adenylyl cyclase/cAMP (cyclic adenosine monophosphate) pathway. However, despite this similarity, β1 receptor activation increases the force of cardiac muscle contraction, while β2 receptor activation inhibits smooth muscle contraction.
To understand why there is a difference in the type of response produced in the same two muscle types, we need to examine the associated signaling cascades.
In the heart, β1 receptor activation leads to the activation of G-proteins, which in turn activate adenylyl cyclase. Adenylyl cyclase then converts ATP (adenosine triphosphate) into cAMP. Increased levels of cAMP activate protein kinase A (PKA), which phosphorylates various proteins involved in cardiac muscle contraction. This phosphorylation ultimately leads to an increase in the force of contraction.
On the other hand, in airway smooth muscle, β2 receptor activation also leads to the activation of G-proteins and adenylyl cyclase. However, the resulting increase in cAMP levels leads to the activation of protein kinase A, which phosphorylates proteins involved in smooth muscle relaxation. This phosphorylation causes a decrease in intracellular calcium levels, leading to smooth muscle relaxation and inhibition of contraction.
Therefore, the difference in the type of response produced in the same two muscle types can be attributed to the specific downstream effects of the signaling cascades. In cardiac muscle, the signaling cascade leads to an increase in the force of contraction, while in airway smooth muscle, it leads to relaxation and inhibition of contraction. This difference is likely due to the specific proteins that are phosphorylated and the subsequent effects on intracellular calcium levels.