The Role of Alpha-1 Adrenergic Receptor in Disease
Adrenergic receptors are a class of G-protein coupled receptors (GPCRs) which are
activated by catecholamines in the central and peripheral nervous systems. Alpha-1 adrenergic receptors (1-AR) are systematic vasoconstrictors: their activation constricts blood vessels by the contraction of vascular smooth muscle. These transmembrane receptors are activated by the binding of epinephrine or norepinephrine, which creates intracellular signals via activation of the G-protein. The G-protein itself is a heterotrimer; it consists of alpha, beta, and gamma subunits (Figure 1). The alpha subunit of the G-protein is capable of binding to guanosine diphosphate (GDP) or guanosine triphosphate (GTP).4 …show more content…
Upon extracellular activation by epinephrine or norepinephrine, the G-protein of the 1-ARs undergoes a conformational change. This change in structure activates the G-alpha subunit, thereby causing it to release the GDP molecule and replace it with GTP. The alpha subunit and the beta-gamma dimer dissociate from each other and from the GPCR; thus allowing free lateral movement within the plasma membrane. The alpha subunit and beta-gamma dimer can both activate or inhibit proteins and enzymes to produce secondary messengers. Most notably in the case of 1-ARs, the activated G-protein primarily targets two kinases: phospholipase C (PLC) and adenylyl cyclase (AC). PLC stimulates the cleavage of inositol substrate phosphatidylinositol 4,5 bisphosphate (PIP2), yielding diacylglycerol (DAG) and inositol triphosphate (IP3). Both of these molecules mediate calcium release and promote the downstream activation of protein kinase C (PKC). Adenylyl cyclase promotes a rise in cAMP levels, which is involved in mediating many cellular functions.4 Activation of particular proteins and second messengers generate an extensive range of signaling …show more content…
Perez and Doze mediated these connections, in which chronic stimulation of 1-ARs yielded depressive-like behavior in mice.5 They also revealed a link between chronic 1-AR activation and reduced anxiety. Schizophrenia is associated with symptoms of psychosis, hallucinations, delusions, and various other symptoms. This disease has been correlated with dysfunction in the prefrontal cortex (PFC). Antipsychotic drugs, which are treatments for schizophrenia, are 1-AR antagonists. In Arsten’s study of cognitive deficits in schizophrenia, activation of secondary messenger, PKC, eventually led to PFC impairment. Conversely, the inhibition of the receptor inhibits PKC, which may help protect cognitive function in schizophrenic
Adrenergic receptors are a class of G-protein coupled receptors (GPCRs) which are
activated by catecholamines in the central and peripheral nervous systems. Alpha-1 adrenergic receptors (1-AR) are systematic vasoconstrictors: their activation constricts blood vessels by the contraction of vascular smooth muscle. These transmembrane receptors are activated by the binding of epinephrine or norepinephrine, which creates intracellular signals via activation of the G-protein. The G-protein itself is a heterotrimer; it consists of alpha, beta, and gamma subunits (Figure 1). The alpha subunit of the G-protein is capable of binding to guanosine diphosphate (GDP) or guanosine triphosphate (GTP).4 …show more content…
Upon extracellular activation by epinephrine or norepinephrine, the G-protein of the 1-ARs undergoes a conformational change. This change in structure activates the G-alpha subunit, thereby causing it to release the GDP molecule and replace it with GTP. The alpha subunit and the beta-gamma dimer dissociate from each other and from the GPCR; thus allowing free lateral movement within the plasma membrane. The alpha subunit and beta-gamma dimer can both activate or inhibit proteins and enzymes to produce secondary messengers. Most notably in the case of 1-ARs, the activated G-protein primarily targets two kinases: phospholipase C (PLC) and adenylyl cyclase (AC). PLC stimulates the cleavage of inositol substrate phosphatidylinositol 4,5 bisphosphate (PIP2), yielding diacylglycerol (DAG) and inositol triphosphate (IP3). Both of these molecules mediate calcium release and promote the downstream activation of protein kinase C (PKC). Adenylyl cyclase promotes a rise in cAMP levels, which is involved in mediating many cellular functions.4 Activation of particular proteins and second messengers generate an extensive range of signaling …show more content…
Perez and Doze mediated these connections, in which chronic stimulation of 1-ARs yielded depressive-like behavior in mice.5 They also revealed a link between chronic 1-AR activation and reduced anxiety. Schizophrenia is associated with symptoms of psychosis, hallucinations, delusions, and various other symptoms. This disease has been correlated with dysfunction in the prefrontal cortex (PFC). Antipsychotic drugs, which are treatments for schizophrenia, are 1-AR antagonists. In Arsten’s study of cognitive deficits in schizophrenia, activation of secondary messenger, PKC, eventually led to PFC impairment. Conversely, the inhibition of the receptor inhibits PKC, which may help protect cognitive function in schizophrenic