Alpha-1 adrenergic receptor
alpha-1 (α) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the G heterotrimeric G protein. α-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α-, α-, and α-adrenergic receptor subtypes. There is no α receptor. At one time, there was a subtype known as α, but it was found to be identical to the previously discovered α receptor subtype. To avoid confusion, naming was continued with the letter D. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α-adrenergic receptors in the central and peripheral nervous systems. The crystal structure  of the α-adrenergic receptor subtype has been determined in complex with the inverse agonist (+)-cyclazosin. Effects. The α-adrenergic receptor has several general functions in common with the α-adrenergic receptor, but also has specific effects of its own. α-receptors primarily mediate smooth muscle contraction, but have important functions elsewhere as well. The neurotransmitter norepinephrine has higher affinity for the α receptor than does the hormone adrenaline. Smooth muscle. In smooth muscle cells of blood vessels the principal effect of activation of these receptors is vasoconstriction. Blood vessels with α-adrenergic receptors are present in the skin , the sphincters of gastrointestinal system, kidney (renal artery) and brain. During the fight-or-flight response vasoconstriction results in decreased blood flow to these organs. This accounts for the pale appearance of the skin of an individual when frightened. It also induces contraction of the internal urethral sphincterof the urinary bladder, although this effect is minor compared to the relaxing effect of β-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to inhibit micturition upon anticipation of a stressful event. Other effects on smooth muscle are contraction in: Neuronal. Activation  of α-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity. Norepinephrine has been shown to decrease cellular excitability in all layers of the temporal cortex, including the primary auditory cortex. In particular, norepinephrine decreases glutamatergic excitatory postsynaptic potentials by the activation of α-adrenergic receptors. Norepinephrine also stimulates serotonin release by binding α1-adrenergic receptors located on serotonergic neurons in the raphe. α1-adrenergic receptor subtypes increase inhibition in the olfactory system, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors. Signaling cascade. α-Adrenergic  receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, G, activates phospholipase C (PLC), which causes phosphatidylinositol to be transformed into inositol trisphosphate (IP) and diacylglycerol (DAG). While DAG stays near the membrane, IP diffuses into the cytosol and to find the IP receptor on the endoplasmic reticulum, triggering calcium release from the stores. This triggers further effects, primarily through the activation of an enzyme Protein Kinase C. This enzyme, as a kinase, functions by phosphorylation of other enzymes causing their activation, or by phosphorylation of certain channels leading to the increase or  decrease of electrolyte transfer in or out of the cell. Activity during exercise. During exercise, α-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β-adrenergic receptors which mediate vasodilation to dominate. In contrast to α-adrenergic receptors, α-adrenergic-receptors in the arterial vasculature of skeletal muscle are more resistant to inhibition, and attenuation of α1-adrenergic-receptor-mediated vasoconstriction only occurs during heavy exercise. Note that only active muscle α-adrenergic receptors will be blocked. Resting muscle will not have its α-adrenergic receptors blocked, and hence the overall effect will  be α-adrenergic-mediated vasoconstriction. Various heterocyclic antidepressants and antipsychotics are α-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediates side effects like orthostatic hypotension, and headaches due to excessive vasodilation.