Why do beta-1 and beta-2 adrenergic receptors result in two completely different effects (though both use Gs pathway)?

Question

$\beta_2$ adrenergic Receptors are $G_s$-coupled 7-TM proteins. Considering that $G_s$ , by activation increases $[\text{cAMP}]_\text{cytosol}$ which inhibits MLCK of smooth muscles (and causes relaxation as in bronchial smooth muscles).

But at the same time, in cardiac myocytes ($\beta_1$), $G_s$ activation activates PK-A (through cAMP) which in-turn activates L-type $\ce{Ca^{2+}}$ channels. Thus there is prolonged plateau phase and positive inotropic and chronotropic effect.

I think these two results are contradictory. Why and how are these two seemingly completely opposite effects mediated through similar signal transduction pathways?

Madamanchi A. Beta-adrenergic receptor signaling in cardiac function and heart failure. Mcgill J Med. 2007;10(2):99-104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323471/

Answer 1

The autonomic nervous system is composed of the parasympathetic and sympathetic nervous systems. The sympathetic nervous system is stimulated via adrenergic receptors.

Adrenergic receptors are G protein-coupled receptors stimulated by norepinephrine (noradrenaline) and epinephrine (adrenaline).

There are 4 sub-types of adrenergic receptors:

• Beta1-adrenergic receptors
• Beta2-adrenergic receptors
• Beta3-adrenergic receptors
• Beta4-adrenergic receptors

Yes, Beta2-adrenergic agonists reduce bronchial Smooth muscle contraction.

Yes, Beta1-adrenergic agonists increase heart rate.

Here we can see activation of different tissues from different receptors, that activate the same pathway. Thus, despite the example explained - the activation of the same path-way - different responses ensue.

• In the human airway - Smooth muscle cells express Beta2-adrenergic receptors the most (100%).

• In human heart tissue (Cardiomyocytes/Cardiac muscle cells), of Beta-adrenergic receptors - Beta1-adrenergic receptors are expressed the most (75–80%).

"...the cAMP pathway generally promotes contraction in cardiac muscle; however, in Smooth muscle, activation of cAMP causes relaxation."

Source

cAMP inhibits myosin light chain kinase, the enzyme that is responsible for phosphorylating Smooth muscle myosin and causing contraction. Thus no contraction takes place in smooth muscles cells.

Inhibition of myosin light chain kinase increases intracellular cAMP, which further inhibits myosin light chain kinase thereby producing a lower contractile force (E.g. promoting relaxation).

Source