Dopamine Receptors From Structure To Function Pdf Free ##TOP##
hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary.
Dopamine Receptors From Structure To Function Pdf Free
Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.
As we know today, hCG is a hormone comprising an α-subunit and a β-subunit which are held together by non-covalent hydrophobic and ionic interactions. The molecular weight of hCG is approximately 36,000. It is an unusual molecule in that 25-41% of the molecular weight is derived from the sugar side-chains (25-30% in regular hCG and 35-41% in hyperglycosylated hCG). Today, the function of hCG is still marked as being progesterone promotion in most medical student text books, but we now know now that hCG has numerous other important placental, uterine and fetal functions in pregnancy. From the time of implantation, hCG produced by trophoblast cells take over corpus luteal progesterone production rom luteinizing hormone (LH), acting on a joint hCG/LH receptor. This continues for approximately 3 to 4 weeks. After that time, there are sufficient syncytiotrophoblast cells in the placenta to take over progesterone production from corpus luteal cells.
The hormone hCG comprises an α-subunit and a β-subunit. The α-subunit is common to hCG, to the autocrine/paracrine hyperglycosylated hCG, to the hormone pituitary hCG, and to the hormones LH, follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH), and to the common free α-subunit formed in excess. The β-subunit of hCG, while structurally somewhat similar to the β-subunit of LH, differentiates hCG, hyperglycosylated hCG, and pituitary hCG from other molecules. Both hCG and LH bind and function through a common hCG/LH receptor. The biggest difference between LH and hCG is that LH, pI 8.0, has a circulating half-life of just 25-30 minutes [15], while hCG, pI 3.5, has a circulating half-life of approximately 37 hours [16], or 80-fold longer than that of LH. In many respects hCG is a super LH produced in pregnancy, with 80X the biological activity of LH, yet acting on the joint receptor. While LH, FSH and TSH are made by the anterior lobe of the pituitary, hCG is produced by fused and differentiated placental syncytiotrophoblast cells [6].
As yet, it is unknown whether there is a specific function for pituitary hCG during the menstrual cycle. Pituitary hCG could have functions separate from those of LH. But even if pituitary hCG has no specific function, there is a natural explanation for its production. There is a single LH β-subunit gene next to the 8 back-to-back hCG β-subunit genes on human chromosome 19 (Figure 1) [137]. hCG and LH share a single common α-subunit. It is possible, as indicated in Figure 1, that hCG β-subunit gene transcription is promoted consequentially by gonadotropin releasing hormone (GnRH) alongside specific LH β-subunit stimulation in pituitary gonadotrope cells during normal menstrual cycle physiology in women and normal physiology in men.
hCG and associated molecules seeming have a wide array of biological activities. hCG and hyperglycosylated hCG effective control placentation and fetal development during pregnancy. Considering these critical biological functions there is a major paradox that exists. That is that individual hCG levels in serum (Table 2) and urine (Table 3) of total hCG and hyperglycosylated hCG vary extremely widely. In serum, in the 4th week of gestation (weeks following start of menstrual period), individual total hCG values vary by 824-fold, between 0.21 and 173 ng/ml amongst different women with singleton term outcome pregnancies (all failing pregnancies removed from table) (Table 2). Hyperglycosylated hCG values vary even wider during this week of pregnancy, 888-fold. In the 5th week of gestation total hCG values vary by 704 fold, between 1.86 and 1308 ng/ml amongst different women with singleton term outcome pregnancies. Hyperglycosylated hCG values vary once again slightly wider, 734-fold. We ask how and why does this extremely wide variation exist with such important molecules between different pregnancies, and how with such extreme variation in signal, can all these pregnancies go to term and produce similar size babies? This is the subject of two articles. The first article addresses the cause of the wide variation [147], and the second article address the affect of the wide variation, or how the receptors cope with this situation [Cole LA, paper submitted to J Clin Endocrinol Metab].
Dopamine is a prototypical neuromodulator that controls circuit function through G protein-coupled receptor signalling. Neuromodulators are volume transmitters, with release followed by diffusion for widespread receptor activation on many target cells. Yet, we are only beginning to understand the specific organization of dopamine transmission in space and time. Although some roles of dopamine are mediated by slow and diffuse signalling, recent studies suggest that certain dopamine functions necessitate spatiotemporal precision. Here, we review the literature describing dopamine signalling in the striatum, including its release mechanisms and receptor organization. We then propose the domain-overlap model, in which release and receptors are arranged relative to one another in micrometre-scale structures. This architecture is different from both point-to-point synaptic transmission and the widespread organization that is often proposed for neuromodulation. It enables the activation of receptor subsets that are within micrometre-scale domains of release sites during baseline activity and broader receptor activation with domain overlap when firing is synchronized across dopamine neuron populations. This signalling structure, together with the properties of dopamine release, may explain how switches in firing modes support broad and dynamic roles for dopamine and may lead to distinct pathway modulation.
How the brain recovers from addiction is an exciting and emerging area of research. There is evidence that the brain does recover; the image below shows the healthy brain on the left, and the brain of a patient who misused methamphetamine in the center and the right. In the center, after one month of abstinence, the brain looks quite different than the healthy brain; however, after 14 months of abstinence, the dopamine transporter levels (DAT) in the reward region of the brain (an indicator of dopamine system function) return to nearly normal function (Volkow et al., 2001).
Neurotransmitters are synthetized in and released from nerve endings into the synaptic cleft. From there, neurotransmitters bind to receptor proteins in the cellular membrane of the target tissue. The target tissue gets excited, inhibited, or functionally modified in some other way.
Excitatory neurotransmitters function to activate receptors on the postsynaptic membrane and enhance the effects of the action potential, while inhibitory neurotransmitters function to prevent an action potential. In addition to the above classification, neurotransmitters can also be classified based on their chemical structure:
The destruction of the substantia nigra leads to the destruction of the only central nervous system source of dopamine. Dopamine depletion leads to uncontrollable muscle tremors seen in patients suffering from Parkinson's disease.
Most often, myasthenia gravis results from circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction. This inhibits the excitatory effects of acetylcholine on nicotinic receptors at neuromuscular junctions. In a much rarer form, muscle weakness may result from a genetic defect in parts of the neuromuscular junction which is inherited, as opposed to developing through passive transmission from the mother's immune system at birth or through autoimmunity later in life.
To foster a better understanding of dopamine receptor functionality, this detailed volume creates an interface between updated classical methods and new emerging technologies heretofore not available to new or seasoned researchers. Divided in five sections dedicated to experimental approaches investigating different facets of dopaminergic signal transduction, Dopamine Receptor Technologies covers epigenetic and post-transcriptional analysis, computational and biochemical techniques, visualization and imaging methods, molecular and cell biological tools, as well as behavioral assessment. The book, as a part of the popular Neuromethods series, provides insightful step-by-step protocols and methodological reviews that readers will find useful.
They are also neuromodulators, meaning that, unlike other neurotransmitters, they are able to communicate with many neurons that are near as well as far away from the dopamine or serotonin release site.
Neurotransmitters do not act independently. They interact with and affect each other to maintain a careful chemical balance within the body. There are strong links between the serotonin and dopamine systems, both structurally and in function.
A medical condition that health experts call dopamine transporter deficiency syndrome or infantile parkinsonism-dystonia occurs when mutations in the SLC6A3 gene affect how the dopamine transporter proteins function. 350c69d7ab