CALCRL
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CALCRL
Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. Function The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor. CALCRL is linked to one of three single transmembrane domain receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CALCRL with different RAMP proteins produces different receptors: * with RAMP1: produces a CGRP receptor * with RAMP2: produces an adrenomedullin (AM) receptor, designated AM1 * with RAMP3: produces a dual CGRP/AM receptor designated AM2 These receptors are linked to the G protein Gs, which activates adenylate cyclase and activation results in the generation of intracellular cyclic adenosine monophosphate (cAMP). CGRP receptors are found throughout the body, suggesting that the protein may modulate a variety of physiological funct ...
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Calcitonin Gene-related Peptide
Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha (α-CGRP or CGRP I), and CGRP beta (β-CGRP or CGRP II). α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY). Function CGRP is produced in both peripheral and central neurons. It is a potent peptide vasodilator and can function in the transmission of nociception. In the spinal cord, the function and expression of CGRP ...
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CGRP
Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha (α-CGRP or CGRP I), and CGRP beta (β-CGRP or CGRP II). α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY). Function CGRP is produced in both peripheral and central neurons. It is a potent peptide vasodilator and can function in the transmission of nociception. In the spinal cord, the function and expression of C ...
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Receptor Activity-modifying Protein
Receptor activity-modifying proteins (RAMPs) are a class of protein that interact with and modulate the activities of several Class B G protein-coupled receptors including the receptors for secretin, calcitonin (CT), glucagon, and vasoactive intestinal peptide (VIP). There are three distinct types of RAMPs in mammals (though more in fish), designated RAMP1, RAMP2, and RAMP3, each encoded by a separate gene. Function Currently, the function of RAMPs is divided into classes of activities. When associated with the Calcitonin receptor (CTR) or Calcitonin receptor-like (CALCRL) (below), RAMPs can change the selectivity of the receptor for a specific hormone. In the cases of the other receptors mentioned, however, there is no evidence that they can do this, but instead function to regulate trafficking of receptors from the ER / golgi to the membrane. These functions appear to be ones where there is redundancy, as neither RAMP1 nor RAMP3 knockout mice (KO) have grossly abnorma ...
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RAMP1
Receptor activity modifying protein 1 is a protein that in humans is encoded by the ''RAMP1'' gene. The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CALCRL) to the plasma membrane. CALCRL, a receptor with seven transmembrane domains, can function as either a calcitonin gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In combination with the RAMP1 protein, CALCRL functions as the CGRP receptor. The RAMP1 protein is involved in the terminal glycosylation, maturation, and presentation of the CGRP receptor to the cell surface. The RAMP1 protein can also interact with the calcitonin receptor (CT) protein, where heterom ...
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Adrenomedullin
Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the adrenal medulla: hence the name. In humans ADM is encoded by the ''ADM'' gene. ADM is a peptide expressed by all tissues, and found in the circulation. A similar peptide named adreomedullin2 was reported in rats in 2004 which exhibits a similar function. Function Adrenomedullin may function as a hormone in the circulation control because it is found in blood in a considerable concentration. It was initially identified as a vasodilator, and some argued that it is the most potent endogenous vasodilatory peptide found in the body. Differences in opinion regarding the ability of AM to relax vascular tone may arise from the differences in the model system used. Other effects of AM include stimulating the growth of new blood vessels (angiogenesis) and increasing the tolerance of cells to oxidative ...
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RAMP2
Receptor activity modifying protein 2, also known as RAMP2, is a protein which in humans is encoded by the ''RAMP2'' gene. Function The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N-terminus and a cytoplasmic C-terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP2) protein, CRLR functions as an adrenomedullin Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the a ...
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RAMP3
Receptor activity modifying protein 3, also known as RAMP3, is a human gene. The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In humans and other mammals, there are 3 RAMPS, while in fish there are more, with sub-variants. In the presence of this (RAMP3) protein, CRLR functions as an adrenomedullin Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a ...
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Calcitonin Gene-related Peptide Receptor Antagonist
Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR). Several monoclonal antibodies which binds to the CGRP receptor or peptide have been approved for prevention of migraine. Three small molecule CGRPR antagonists are approved in the U.S. as antimigraine agents. Drugs of this class have also been investigated for use in osteoarthritis. Examples Non-peptide small molecules * Ubrogepant is approved for acute treatment of migraines *Rimegepant (BMS-927711) is approved for acute and preventative treatment of migraines * Atogepant (AGN-241689) is approved for preventative treatment of migraines *Telcagepant (MK-0974), reached phase III clinical trials; development discontinued in 2011. *Olcegepant (BIBN-4096BS) is a drug candidate * BI 44370 TA (BI 44370) * MK-3207 * SB-268262 Monoclonal antibodies targeting the CGRP receptor * Erenumab (AMG-334) is approved for prevention of ...
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Nerve Cells
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells. Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. When multiple neurons are connected together, they form what is called a neural circuit. A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is a compact structure, and the axon and dendrite ...
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Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding. If injected intravenously, it may cause cerebral effects such as confusion, changes in vision, numbness, tingling, and vomiting. It can cause low blood pressure and an irregular heart rate. There are concerns that injecting it into a joint can cause problems with the cartilage. It appears to be generally safe for use in pregnancy. A lower dose may be required in those with liver problems. It is generally safe to use in those ...
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Botox
Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. The toxin causes the disease botulism. The toxin is also used commercially for medical and cosmetic purposes. The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G). New types are occasionally found. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals. Botulinum toxins are among the most potent toxins known. Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. The estimated human lethal dose of type A toxin is ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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