Major Receptors
This article has been published by the International Biopharmaceutical Association www.ibpassociation.org
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A receptor is a binding or recognition site with a specific molecular configuration on a cell surface or within the cell structure, which causes a physiologic response upon stimulation by an NT or other chemical, such as a drug or toxin. Some receptors cause inhibitory (e.g., relaxation of a muscle) or excitatory (e.g., initiation of nerve impulse or contraction of a muscle) responses. Usually, movement of Na+ depolarizes and is stimulatory, whereas movement of Cl¯ hyperpolarizes and is inhibitory.
Ion channel receptors can be classified into receptors that are channel (e.g., nicotine, GABA, glycine, and glutamate receptors) or second messenger receptors that are activated by a second messenger to affect the channel (e.g., adrenergic, muscarinic, serotonergic, and dopaminergic receptors).
Receptors are continuously synthesized in the cell body, transported to the respective sites, stored in the membrane, and after use degraded. Their half-lives range from days to weeks. The number of receptors and their affinity for specific NT molecules is not constant. Receptors that are continuously stimulated by NTs or drugs (agonists) become hyposensitive ("down-regulation"), whereas receptors that are not stimulated by their NT or are blocked by drugs (antagonists) become hypersensitive ("up-regulation"). Up-regulation or down-regulation of receptors plays a major role in the development of tolerance and physical dependence (pharmacodynamic tolerance or dependence). Withdrawal is usually a rebound phenomenon due to an altered receptor affinity and/or density.
Most NTs interact primarily with the postsynaptic receptor (R-1) to produce a physiologic response in the adjacent structure. However, receptors are also located on presynaptic neurons and control the release of a specific NT. These receptors can be divided into different classes. The autoreceptors (R-2) respond only to released NT and are of 2 types: (R-2,+) that increase the release of NT, and (R-2,) that inhibit the release of NT. Presynaptic receptors (R-3) can increase or inhibit the release of an NT. In addition, receptors for neuromodulators (R-4) or substances that are not released from nerve terminals (e.g., steroids, prostaglandins) can modulate the release of the NT.
Cholinergic receptors can be divided into nicotinic N1 (adrenal medulla, autonomic ganglia) and N2 (skeletal muscle) receptors as well as muscarinic M1 (autonomic system, striatum, cortex, hippocampus) and M2 (autonomic system, heart, intestinal smooth muscle, hindbrain, cerebellum) receptors
Adrenergic receptors can be divided into alpha1 (postsynaptic in the sympathetic system) and alpha2 (presynaptic in the sympathetic system and postsynaptic in the brain) receptors, as well as β-1 (heart) and β-2 (other sympathetically innervated structures) receptors.
Dopaminergic receptors can be classified as D1, D2, and D3 receptors. D1 receptors activate adenylate cyclase via stimulatory G-proteins, whereas D2 receptors inhibit this enzyme via inhibitory G-proteins. D1 receptors are more frequent than D2 receptors (4:1), but both receptors are formed in the same brain areas (e.g., limbic region, basal ganglia). The D3 receptor does not seem to affect adenylate cyclase and is more localized in the limbic areas. In addition, isoforms of the individual receptors have been detected.
GABA receptors can be divided into GABAA receptors activating chloride channels, or GABAB receptors potentiating adenosine 3,5-cyclic phosphate (cAMP) formation. This site can be influenced by benzodiazepines (eg, benzodiazepine binding increases GABA binding), barbiturates, picrotoxin, or muscimol.
Serotonin (5-HT) receptors can be divided into 5-HT1, 5-HT2, and 5-HT3 receptors.
Glutamate receptors (excitatory) can be subclassified as N-methyl-D-aspartate (affecting the flow of Na+, K+, Ca+ +), quisqualate (Na+, K+), and kainate (Na+, K+) receptors.
Endorphin-enkephalin or opioid receptors can be divided into µ1 and µ2 (sensorimotor integration, analgesia), delta (motor integration, cognitive function), and kappa 1 and kappa 2 (water balance regulation, analgesia, food intake). All receptors are inhibitory in nature, are often located presynaptically, and seem to be coupled to G-proteins.
For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)
The project is sponsored by KRC CRO and training services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )
Start your Clinical Research Career Now
A receptor is a binding or recognition site with a specific molecular configuration on a cell surface or within the cell structure, which causes a physiologic response upon stimulation by an NT or other chemical, such as a drug or toxin. Some receptors cause inhibitory (e.g., relaxation of a muscle) or excitatory (e.g., initiation of nerve impulse or contraction of a muscle) responses. Usually, movement of Na+ depolarizes and is stimulatory, whereas movement of Cl¯ hyperpolarizes and is inhibitory.
Ion channel receptors can be classified into receptors that are channel (e.g., nicotine, GABA, glycine, and glutamate receptors) or second messenger receptors that are activated by a second messenger to affect the channel (e.g., adrenergic, muscarinic, serotonergic, and dopaminergic receptors).
Receptors are continuously synthesized in the cell body, transported to the respective sites, stored in the membrane, and after use degraded. Their half-lives range from days to weeks. The number of receptors and their affinity for specific NT molecules is not constant. Receptors that are continuously stimulated by NTs or drugs (agonists) become hyposensitive ("down-regulation"), whereas receptors that are not stimulated by their NT or are blocked by drugs (antagonists) become hypersensitive ("up-regulation"). Up-regulation or down-regulation of receptors plays a major role in the development of tolerance and physical dependence (pharmacodynamic tolerance or dependence). Withdrawal is usually a rebound phenomenon due to an altered receptor affinity and/or density.
Most NTs interact primarily with the postsynaptic receptor (R-1) to produce a physiologic response in the adjacent structure. However, receptors are also located on presynaptic neurons and control the release of a specific NT. These receptors can be divided into different classes. The autoreceptors (R-2) respond only to released NT and are of 2 types: (R-2,+) that increase the release of NT, and (R-2,) that inhibit the release of NT. Presynaptic receptors (R-3) can increase or inhibit the release of an NT. In addition, receptors for neuromodulators (R-4) or substances that are not released from nerve terminals (e.g., steroids, prostaglandins) can modulate the release of the NT.
Cholinergic receptors can be divided into nicotinic N1 (adrenal medulla, autonomic ganglia) and N2 (skeletal muscle) receptors as well as muscarinic M1 (autonomic system, striatum, cortex, hippocampus) and M2 (autonomic system, heart, intestinal smooth muscle, hindbrain, cerebellum) receptors
Adrenergic receptors can be divided into alpha1 (postsynaptic in the sympathetic system) and alpha2 (presynaptic in the sympathetic system and postsynaptic in the brain) receptors, as well as β-1 (heart) and β-2 (other sympathetically innervated structures) receptors.
Dopaminergic receptors can be classified as D1, D2, and D3 receptors. D1 receptors activate adenylate cyclase via stimulatory G-proteins, whereas D2 receptors inhibit this enzyme via inhibitory G-proteins. D1 receptors are more frequent than D2 receptors (4:1), but both receptors are formed in the same brain areas (e.g., limbic region, basal ganglia). The D3 receptor does not seem to affect adenylate cyclase and is more localized in the limbic areas. In addition, isoforms of the individual receptors have been detected.
GABA receptors can be divided into GABAA receptors activating chloride channels, or GABAB receptors potentiating adenosine 3,5-cyclic phosphate (cAMP) formation. This site can be influenced by benzodiazepines (eg, benzodiazepine binding increases GABA binding), barbiturates, picrotoxin, or muscimol.
Serotonin (5-HT) receptors can be divided into 5-HT1, 5-HT2, and 5-HT3 receptors.
Glutamate receptors (excitatory) can be subclassified as N-methyl-D-aspartate (affecting the flow of Na+, K+, Ca+ +), quisqualate (Na+, K+), and kainate (Na+, K+) receptors.
Endorphin-enkephalin or opioid receptors can be divided into µ1 and µ2 (sensorimotor integration, analgesia), delta (motor integration, cognitive function), and kappa 1 and kappa 2 (water balance regulation, analgesia, food intake). All receptors are inhibitory in nature, are often located presynaptically, and seem to be coupled to G-proteins.
For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)
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