Subtypes nature

Rudolph U, Crestani F, Benke D et al (1999) Benzodiazepine actions mediated by specific y-aminobutyric acidA receptor subtypes. Nature 401 796-800... 

Smithies, O., Connell, G. E., and Dixon, G. H., Inheritance of haptoglobin subtypes. Nature In press. 

Luo L, Salunga RC, Guo H, Bittner A, Joy KC, et al. 1999. Gene expression profiles of laser-capture adjacent neuronal subtypes. Nature Med 5 117. 

Riban V, Bouilleret V, Pham-L BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112 101-111 Rudolph U, Crestani F, Benke D, Brunig I, Benson J, Fritschy JM, Martin JR, Bluethmann H, Mohler H (1999) Benzodiazepine actions mediated by specific y-aminobutyric acid A receptor subtypes. Nature 401 796-800... 

K. Fukuda, T. Kubo, I. Akiba, A. Maeda, M. Mishrma, S. Numa (1987). Molecular distinction between muscarinic acetylchoUne receptor subtypes. Nature 527 623-625. 

Liu SQ, Cull-Candy SG (2000) Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405 454-458. 

Fukuda K, Kubo T, Akiba I, Maeda A, Mishina M, Numa S (1987) Molecular distinction between muscarinic acetylcholine receptor subtypes. Nature 327(6123) 623-625... 

Acetyl choline is the natural neurotransmitter for the cholinergic receptor. Two distinct receptor subtypes have been characterized based on their binding affinity for either nicotine (189) and (190) or muscarine (191). 

Receptor subtype Most potent natural PG agonist Usual response on smooth muscle... 

The concept of chemical periodicity is central to the study of inorganic chemistry. No other generalization rivals the periodic table of the elements in its ability to systematize and rationalize known chemical facts or to predict new ones and suggest fruitful areas for further study. Chemical periodicity and the periodic table now find their natural interpretation in the detailed electronic structure of the atom indeed, they played a major role at the turn of the century in elucidating the mysterious phenomena of radioactivity and the quantum effects which led ultimately to Bohr s theory of the hydrogen atom. Because of this central position it is perhaps not surprising that innumerable articles and books have been written on the subject since the seminal papers by Mendeleev in 1869, and some 700 forms of the periodic table (classified into 146 different types or subtypes) have been proposed. A brief historical survey of these developments is summarized in the Panel opposite. 

Richardson, B. P., Engel, G., Donatsch, P., and Stadler, P. A. (1985). Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316 126-131. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

Lynch DR, Guttmann RP (2002) Excitotoxicity perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 300(3) 717-723 Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995) Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37(3) 373-380 Mamdouh Z, Chen X, Kerini LM, Maxfield FR, Muller WA (2003) Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis. Nature 421(6924) 748-753... 

Kaupmann, K, Malitschek, B, Schuler, V, Held, J, Froestl, W, Beck, P, Mosbacher, J, Bischoff, S, Kulik, A, Shigemoto, R, Karschin, A and Bettler, B (1998) GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature 396 683-687. 

It is important to note that most molecules are not rigid but may prefer a distrinct structure and the conformation of a molecule strongly depends on its specific environment. Hence, the crystal structure of a drug does not have to correspond to the receptor bound conformation. Also, a conformation in solution depends on the nature of the solvent and measuring conditions, and may change when the molecule is bound to the receptor [4]. In addition, different receptors or receptor subtypes can bind the same drug in different conformations. It is a general assumption and observation, but by far not a strict condition, that the conformation in aqueous solution is similar to the bound conformation and is a better representation of the bioactive conformation than an X-ray structure of the isolated molecule in the crystalline state. 

Kaupmann K, Malitschek B, Schuler V, et al. GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 1998 396(6712) 683—687. 

The issues that, according to these authors, should be included in research conducted in order to reach an understanding of the holistic nature of culture-bound syndromes are as follows identifying the nature of the phenomenon, situating the syndrome within the social context, the relation between the syndrome and the psychiatric disorders included in current classifications, and the social and psychiatric history of the syndrome. By following these steps it will be possible to correctly identify the phenomenology and subtypes of the syndrome, the social characteristics of the people who suffer from it and the risk factors, as well as to study the relation with other psychiatric disorders and even other syndromes that are specific to other cultures. 

---