Which of the following steps in a signaling pathway typically occurs first once a chemical messenger reaches a target cell?
IntroductionCell to cell communication is critical for the survival of an organism. Cells can communicate through a process called signal transduction pathway. When sending a signal, different molecules, such as hormones, can bind to a receptor on or inside the cell membrane, leading to chemical reactions in the cell ultimately reaching the target. Cells use a second messenger to transmit these messages. Show
This article will be discussing the different types of receptors, focusing specifically on dopamine receptors, the different types of dopamine receptors, and what function each receptor has. The article will also go into different illnesses and medications that target these receptors. The dopamine receptors affect many various functions, ranging from hypertension and hormonal regulation to voluntary movement and reward.[1] FundamentalsThere are many different types of signaling receptors in the human body, with the majority being the G-protein coupled receptors (GPCRs). GPCRs have an intracellular C-terminus and an extracellular N-terminus. GPCRs are also known as the seven-pass transmembrane proteins; this is because the receptor consists of seven sequential helices that cross the transmembrane, allowing the receptor to correctly insert into the cell membrane and couple with the G protein. This coupling permits the receptor to modulate signaling cascades. The dopamine receptor is a type of G-protein coupled receptor. Dopamine receptors can also act through G-protein independent mechanisms such as ion channel interactions. Dopamine is a monoamine catecholamine neurotransmitter and hormone. It binds to the dopamine receptor, and depending on the type of receptor, has many different functions. Dopamine receptors are mostly present in the central nervous system.[2] CellularThe dopamine receptors are located and encoded by different genes. D1 receptor encoding is by the gene, 5q31-q34. The D2 receptor is on chromosome 11, along with the D4 receptor, while the D3 receptor is located on the third chromosome. The D5 receptor is on the fourth chromosome.[2][3] FunctionDopamine receptors play an essential role in daily life functions. This hormone and its receptors affect movement, emotions and the reward system in the brain. Dopamine receptors are expressed in the central nervous system, specifically in the hippocampal dentate gyrus and subventricular zone. Dopamine receptors are also expressed in the periphery, more prominently in kidney and vasculature, There are five types of dopamine receptors, which include D1, D2, D3, D4, and D5. Each receptor has a different function. The function of each dopamine receptor[4]:
PathophysiologyThe five different dopamine receptors can subdivide into two categories. D1 and D5 receptors group together, and D2, D3, D4 are together in a separate subgrouping. D1 and D5 receptors couple to G stimulatory sites and activate adenylyl cyclase. The activation of adenylyl cyclase leads to the production of the second messenger cAMP, which leads to the production of protein kinase A (PKA) which leads to further transcription in the nucleus. D2 through D4 receptors couple to G inhibitory sites, which inhibit adenylyl cyclase and activate K+ channels. The D1 receptor is the most abundant out of the five in the central nervous system, followed by D2, then D3, D5 and least abundant is D4. D1 receptors help regulate the development of neurons when the dopamine hormone binds to it. D1 and D5 receptors have high density in the striatum, nucleus accumbens, olfactory bulb, and substantia nigra. These receptors are essential in regulating the reward system, motor activity, memory, and learning. D1 and D5 receptors, along with stimulating adenyl cyclase, also activate phospholipase C, which leads to the induction of intracellular calcium release and activation of protein kinase C. Protein kinase C is a calcium-dependent protein kinase. Calcium is also involved in modulating neurotransmitter release by exocytosis. D1 and D5 receptors are also involved in the kidney by inhibiting Na/K ATPase through PKA and PKC pathways. In the kidney, these receptors correlate with an increase in electrolyte excretion and renal vasodilation. D2, D3, and D4 receptors are expressed mainly in the striatum, as well as the external globus pallidus, core of nucleus accumbens, hippocampus, amygdala, and cerebral cortex. These receptors also affect the postsynaptic receptor-medicated extrapyramidal activity. D2-D4 receptors are important in the signaling for the survival of human dopamine neurons and neuronal development.[4][5] Clinical SignificanceMany different diseases involve increased or decreased dopamine leading to different effects. The two primary conditions discussed here along with the pharmacology targeting dopamine receptors are Parkinson disease and schizophrenia. Parkinson disease[6][7]:
Schizophrenia[8][9][10][9]:
Review QuestionsReferences1.Beaulieu JM, Espinoza S, Gainetdinov RR. Dopamine receptors - IUPHAR Review 13. Br J Pharmacol. 2015 Jan;172(1):1-23. [PMC free article: PMC4280963] [PubMed: 25671228] 2.Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, Reed L, Magenis RE, Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. Am J Hum Genet. 1989 Nov;45(5):778-85. [PMC free article: PMC1683432] [PubMed: 2573278] 3.Grandy DK, Allen LJ, Zhang Y, Magenis RE, Civelli O. Chromosomal localization of three human D5 dopamine receptor genes. Genomics. 1992 Aug;13(4):968-73. [PubMed: 1387108] 4.Mishra A, Singh S, Shukla S. Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson's disease. J Exp Neurosci. 2018;12:1179069518779829. [PMC free article: PMC5985548] [PubMed: 29899667] 5.Vekshina NL, Anokhin PK, Veretinskaya AG, Shamakina IY. [Heterodimeric D1-D2 dopamine receptors: a review]. Biomed Khim. 2017 Jan;63(1):5-12. [PubMed: 28251946] 6.Gilat M, Bell PT, Ehgoetz Martens KA, Georgiades MJ, Hall JM, Walton CC, Lewis SJG, Shine JM. Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease. Neuroimage. 2017 May 15;152:207-220. [PubMed: 28263926] 7.You H, Mariani LL, Mangone G, Le Febvre de Nailly D, Charbonnier-Beaupel F, Corvol JC. Molecular basis of dopamine replacement therapy and its side effects in Parkinson's disease. Cell Tissue Res. 2018 Jul;373(1):111-135. [PubMed: 29516217] 8.Howes OD, McCutcheon R, Owen MJ, Murray RM. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biol Psychiatry. 2017 Jan 01;81(1):9-20. [PMC free article: PMC5675052] [PubMed: 27720198] 9.Tardy M, Huhn M, Engel RR, Leucht S. Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2014 Aug 03;(8):CD009230. [PubMed: 25087165] 10.Seeman P. An update of fast-off dopamine D2 atypical antipsychotics. Am J Psychiatry. 2005 Oct;162(10):1984-5. [PubMed: 16199855] What is the first step in a signaling pathway?Step 1: Reception
Signal reception is the first step of cell signaling and involves the detection of signaling molecules originating from the extracellular environment. Here, the molecules (ligands) are detected when they bind to the cell receptors.
What is the correct order of a cell signaling pathway?Three Stages of Cell Signaling
First, reception, whereby the signal molecule binds the receptor. Then, signal transduction, which is where the chemical signal results in a series of enzyme activations. Finally, the response, which is the resulting cellular responses.
Which of the following is the first messenger in any Signalling pathway?First messengers are extracellular signaling molecules such as hormones or neurotransmitters that bind to cell-surface receptors and activate intracellular signaling pathways.
What happens first when a chemical messenger reaches a target cell?First, a chemical signal is released from the signaling cell into the extracellular environment. Second, the chemical signal is transported through the extracellular environment to the target cell. Third, the chemical signal binds to a receptor on the target cell, thus communicating the signal.
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