CAMP-dependent Pathway - Activation

Activation

Activated GPCRs cause a conformational change in the attached G protein complex, which results in the G_s alpha subunit's exchanging GDP for GTP and separation from the beta and gamma subunits. The G_s alpha subunit, in turn, activates adenylyl cyclase, which quickly converts ATP into cAMP. This leads to the activation of the cAMP-dependent pathway. This pathway can also be activated downstream by directly activating adenylyl cyclase or PKA.

Molecules that activate cAMP pathway include:

• cholera toxin - increase cAMP levels
• forskolin - a diterpene natural product that activates adenylyl cyclase
• caffeine and theophylline inhibit cAMP phosphodiesterase, which leads to an activation of G proteins that result in the activation of the cAMP pathway
• bucladesine (dibutyryl cAMP, db cAMP) - also a phosphodiesterase inhibitor
• pertussis toxin, which increase cAMP levels by inhibiting Gi to its GDP (inactive) form. This leads to an increase in adenylyl cyclase, therefore increasing cAMP levels, which can lead to an increase in insulin and therefore hypoglycemia