Effect of Beta Receptor Activation on Smooth Muscle

(Results of PKA Phosphorylation in Smooth Muscle)

  1. Agonist binds to the myocardial beta1-adrenergic receptor. This receptor is a typical G-protein coupled receptor with 7 membrane spanning regions.

  2. In the unstimulated state the G-protein is complexed with GDP.

  3. The receptor promotes exchange of GTP for GDP and release of G"/GTP.

  4. The G"/GTP complex activates adenylate cyclase.

  5. Intracellular cAMP increases and activates cAMP dependent protein kinase (PKA).

  6. PKA phosphorylates the Ca2+ channel promoting Ca2+ influx.

  7. sarcolemma - Decrease Ca2+ influx, increase Ca2+ efflux

  8. sarcoplasmic reticulum - Enhance Ca2+ uptake

  9. decrease actin-myosin interactions - muscle relaxation

  10. G" directly activates the Ca2+ channel.

  11. Prolonged stimulation can lead to receptor down regulation via PKA and other protein kinases which phosphorylate the receptor. The other protein kinases which are involved in phosphorylation are referred to as G-protein coupled receptor kinases or GRKS. These phosphorylation steps lead to internalization of the receptor.

    12.

Previous Page