Mechanisms involved in alpha-adrenergic phenomena.
Epinephrine and norepinephrine exert many important actions by interacting with alpha 1- and alpha 2-adrenergic receptors in their target cells. Activation of alpha 2-adrenergic receptors causes platelet aggregation and other inhibitory cellular responses. Some of these responses are attributable to a decrease in cAMP due to inhibition of adenylate cyclase. Activation of alpha 2-adrenergic receptors promotes their coupling to an inhibitory guanine nucleotide binding protein (Ni). This coupling promotes the binding of GTP to Ni, causing it to dissociate into subunits. This results in inhibition of the catalytic component of adenylate cyclase. Activation of alpha 1-adrenergic receptors stimulates the contraction of most smooth muscles and alters secretion and metabolism in several tissues. The primary event is a breakdown of phosphatidylinositol-4,5-bisphosphate in the plasma membrane to produce two intracellular "messengers": myo-inositol-1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG). IP3 causes the release of Ca2+ from endoplasmic reticulum, producing a rapid rise in cytosolic Ca2+. Ca2+ binds to the regulatory protein calmodulin, and the resulting complex interacts with specific or multifunctional calmodulin-dependent protein kinases and other calmodulin-responsive proteins, altering their activities and thereby producing a variety of physiological responses. DAG also produces effects by activating a Ca2+-phospholipid-dependent protein kinase (protein kinase C) that phosphorylates and alters the activity of certain cellular proteins. Frequently there is synergism between the IP3 and DAG mechanisms.
Exton
J H
JH
D000262:Adenylyl Cyclases / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D004075:Diglycerides / Q000378:metabolism*; D004837:Epinephrine / Q000502:physiology*; D005989:Glycerides / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013403:Sugar Phosphates / Q000378:metabolism*
C011439:1,2-diacylglycerol; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004075:Diglycerides; D005989:Glycerides; D006150:Guanine Nucleotides; D007295:Inositol Phosphates; D007473:Ion Channels; D008112:Liver Glycogen; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine