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 Alpha-Adrenergic Signaling Pathway

The catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) are agonists for a family of G-protein coupled receptors (GPCRs) known as adrenergic receptors. There are three subfamilies of adrenergic receptors: alpha1 (a1), alpha2 (a2) and beta (b). The alpha1 subfamily contains at least three isotypes: Alpha1A (Alpha1AAR) (a1A); Alpha1B (Alpha1BAR) (a1B); and Alpha1D (Alpha1DAR) (a1D). The alpha2 subfamily contains at least three isotypes: Alpha2A (Alpha2AAR); Alpha2B (Alpha2BAR); and Alpha2B-like.

Adrenergic receptors are GPCRs that link to trimeric G-protein. Specificity of response to catecholamines is mediated in part by the specific Galpha subunit of the G-protein with which it associates. Alpha1 adrenergic receptors favor interaction with heterotrimeric G-proteins that contain the Galphaq/11/14/16 (Gq) (G11) (G14) (G16) subunits. The Galphaq subunit is a primary activator of phospholipase C (PLC). Activation of PLC promotes the cleavage of the inositol substrate phosphatidyl-inositol 4,5 bisphosphate (PIP2) to yield diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG and IP3 promote the activation of a protein kinase Cs (PKC). Alpha1 adrenergic receptors can also activate specific adenylate (adenylyl) cyclases (AC) leading to an increase in cAMP levels. The G-protein mediation of adenylate cyclase is likely to involve Galphas (Gs) and/or Galphai (Gi). The activation of specific PLCs and ACs requires a complex balance of signals from G-proteins, especially the Galpha subunits, within specific cell contexts. DAG and cAMP are second messengers that affect a wide array of cell signaling pathways and responses.