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Adrenergic Receptors Chris Garcia Ryan Roberts Adrenergic Receptors Have 4 Main Subtypes And Are Located At The Synapse Of Postganglionic Nerves Postsynaptic: α1 , β1 , β2 4 Subtypes: α1 , α2 , β1 , β2 Presynaptic: α2 Class of G-Coupled Protein Receptors Target of catecholamines Catechol + Amine side chain Norepinephrine Epinephrine Isoprenaline Dopamine Sympathetic Nervous System Response When catecholamines bind to the adrenergic receptors, generally the sympathetic nervous system is stimulated. α1 Receptor: smooth muscle contraction - Most sensitive to Norepinephrine > Epinephrine >> Isoprenaline - Gq protein coupled -- PLC activated, cleaves PIP2 -- PIP2 increases IP3 and DAG -- IP3 acts on calcium channels leading to contraction of smooth muscle -- Contraction: Dilation of eyes, Urethral sphincter, Erector pili muscles, Uterus -- Vasoconstriction: increased vascular resistance, blood pressure -- Glycogenolysis and gluconeogenesis from adipose tissue and liver -- Na+ reabsorption from kidney -- Sweat gland secretion α2 Receptor: Inhibition - Most sensitive to Epinephrine ≥ Norepinephrine >> Isoprenaline - Gi protein coupled -- Adenylate cyclase inactivated -- AC catalyzes the cyclization of ATP and produces cAMP -- Deactivation of cAMP dependent pathway leads to: -Inhibition of insulin release in the pancreas -Inhibition of norepinephrine through negative feedback -Inhibition of acetalcholine release in parasympathetic NS -Induction of glucagon release from the pancreas -Increased thrombocyte aggregation β1 Receptor: Heart - Most sensitive to Isoprenaline > Norepinephrine = Epinephrine - Gs protein coupled -- Adenylate cyclase activated -- AC catalyzes the cyclization of ATP and produces cAMP -- Activation of cAMP dependent pathway leads to: -Increased chronotropy: speed at which heart beats -Increased inotropy: force at which heart beats -Increased dromotropy: speed of conduction through the heart -Increased renin secretion in kidneys -Increased ghrelin secretion in stomach β2 Receptor: Lungs - Most sensitive to Isoprenaline > Norepinephrine = Epinephrine - Gs protein coupled -- Adenylate cyclase activated -- AC catalyzes the cyclization of ATP and produces cAMP -- Activation of cAMP dependent pathway leads to: -Bronchodilation: Smooth muscle relaxation in bronchi -Vasodilation -Inhibit histamine-release from mast cells -Stimulates insulin secretion -Relaxes non pregnant uterus, bladder wall muscles, bronchioles -Contract sphincters of GI tract -Lipolysis in adipose tissue -Glycogenolysis and gluconeogenesis α1 Receptor Integration The Inositol Phospholipid (IP3) Dependent Pathway is used as a signal transduction pathway for many hormones including: -antidiuretic hormone (ADH): Induces the synthesis and release of glucocorticoids in adrenal cortex of kidney - Thyrotropin-releasing hormone (TRH): Induces the synthesis and release of TSH in anterior pituitary gland - Thyroid-stimulating hormone (TSH): Induces the synthesis and release of a small amount of thyroxine in the thyroid - Angiotensin II: Induces synthesis and release of Aldosterone in adrenal cortex of kidney -Gonadotropin-releasing hormone (GnRH): Induces the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in anterior pituitary gland α Receptor Signaling β Receptor Signaling References "Adrenergic Receptor." Wikipedia. Wikimedia Foundation. Web. <https://en.wikipedia.org/wiki/Adrenergic_receptor>. "QIAGEN - GeneGlobe Pathways - Beta-Adrenergic Signaling." QIAGEN - GeneGlobe Pathways - Beta-Adrenergic Signaling. Web. <https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=56>. "QIAGEN - GeneGlobe Pathways - Alpha-Adrenergic Signaling." QIAGEN - GeneGlobe Pathways - Alpha-Adrenergic Signaling. Web. <https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=27>. David L. Nelson, Albert L. Lehninger, and Michael M. Cox. Lehninger Principles of Biochemistry 5th Ed. New York: W.H. Freeman, 2008. Print. MedImmersion. "The Adrenergic Receptors." YouTube. YouTube, 2015. Web. <https://www.youtube.com/watch?v=Ip1o57qIoZw>.
