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Gli Pro

Substance P, Analogs and Fragments
Definition
Substance P (SP) an undecapeptide, is abundant both in the periphery and in the CNS, where it is usually co-localised with one of the classical neurotransmitters, most commonly serotonin (5- HT) 1.
Related Peptides
SP belongs to a family of neuropeptides known as tachykinins that share the common C-terminal sequence: Phe-X-Gly-Leu-Met-NH2. The three most common tachykinins are SP, neurokinin A (NKA), and neurokinin B (NKB); their biologic actions are mediated through specific cell-surface receptors designated NK1, NK2, and NK3, with SP the preferred agonist for NK1 receptors, NKA for NK2 receptors, and NKB for NK3 receptors 2.
Discovery
SP was originally discovered in 1931 by von Euler and Gaddum as a tissue extract that caused intestinal contraction in vitro; its biologic actions and tissue distribution were further investigated over subsequent decades 3.
Structural Characteristics
SP is an 11-residue neuropeptide with the sequence Arg-Pro-Lys-Pro-Gln-Glin-Phe-Gly-Leu-Met-NH2) 4. In a study, the C- and N-terminal fragments of SP were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity 5. The results obtained, indicated that while the carboxy terminal of SP is essential for peptide bronchoactivity, loss of amino terminal peptides (up to four residues) actually enhances bronchoconstrictor responses to the peptide. Part of this enhancement appears to result from differences in the enzymatic degradation of SP and SP5-11. The data suggest that cleavage of SP by dipeptidyl aminopeptidases could enhance its bioactivity 6. SP analogs: Senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11)), a selective analog for the NK-3 (SP-N) receptor, is 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells 7. Effects of five SP analogs on the licking, biting and scratching response induced by neurokinin (NK) 1 receptor agonists such as SP, physalaemin and (p-Glu6,Pro9)-SP (6-11) (septide) were studied after intrathecal injections in mice. Peptide brought about a SP-like behavioral response, and was approximately 25 times more potent than the D-Pro9 analog, D-septide. Septide-induced response was significantly reduced by lower doses of (D-Arg1, D-Pro2,4, D-Phe7, D-His9, Leu11)-SP than (D- Phe7, D-His9, Leu11)-SP (6-11). In contrast, (D-Arg1, D-Pro2,4, D-Phe7, D-His9)-SP (0.5-1.0 nmol) and (D-Phe7, D-His9)-SP (6-11) (0.5-2.0 nmol) inhibited only SP-induced behavioral response, but not physalaemin- or septide-induced response. The results of this study indicate that NK-1 receptor agonists are not necessarily affected to a same degree by SP analogs containing D-His 8. Analogues of substance P, [D-Arg1,D-Phe5,D-Trp7,9,Leu11] SP (SpD) and [Arg6,D-Trp7,9,NmePhe8]substance P can inhibit neuropeptide-stimulated Ca2+ mobilization, tyrosine phosphorylation, and ERK activation . Crucially, SpD and [Arg6,D-Trp7,9,NmePhe8] SP inhibit SCLC cell growth in vivo and in vitro and stimulate SCLC cell apoptosis. SP analogues were characterized originally as "broad spectrum neuropeptide antagonists" 9.
Mode of Action
The SP receptor is a G protein-coupled receptor, in many respects similar to other well-studied receptors in psychiatry, particularly monoamine receptors 2. The interaction of SP with its receptor activates Gq, which in turn activates phospholipase C to break down phosphatidyl inositol bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on specific receptors in the sarcoplasmic reticulum to release intracellular stores of Ca2+, while DAG acts via protein kinase C to open L-type calcium channels in the plasma membrane. The rise in intracellular [Ca2+] induces the tissue response. With an array of actions as diverse as that seen with SP, there is scope for numerous therapeutic possibilities 10.
Functions
In the central nervous system, SP is associated with the regulation of mood disorders, anxiety, stress, reinforcement, neurogenesis, neurotoxicity and pain. In the digestive tract, SP, along with some other tachykinins, are neurotransmitters that regulate motor activity, secretion of ions and fluid, as well as vascular functions 11, 12.
About the Author
Bio-Synthesis Inc. a leading provider for Custom Antibody, Custom Peptide Synthesis, Custom siRNA Synthesis, Organic Laboratory Technique, Antibiotic Peptides.
My son is interested in buying a Volkswagen Jetta. Are there any model years or styles he should avoid?
My son has his heart set on a manual-transmission, used Jetta, costing less than $12,000. I know that they come in a variety of styles (GLI, GLS, etc), but don't know the advantages of any of them. Could you share your knowlege regarding safety, reliability, parts repair/expense, gas mileage,,, He is getting out of a no-win situation with an Audi and we haven't been able to persuade him to buy American or Asian. Aarrrgh! Anyway, I would appreciate any Jetta pros and cons you can pass along. Thank you!
I set off on a similar quest in 2000 and ended up with a new 2001 VW Golf GL TDI. The Jetta has the same platform and shares most of the same parts as the Golf except for body panels. Essentially the same car but sightly heavier. I still drive my Golf every day and have accumulated 212000 miles on it. I do much of the routine maintenance myself. It is expensive to have a dealer do the simple things (I think that's why the term "stealership" is used.). My car has been plagued with broken plastic things like cup holders, glove box door, window cranks and engine belly pan but engine, transmission and suspension components have held up well. My car is the diesel with manual trans. It smokes, stinks and coughs up blood on cold morning starts but I put up with it because of the mileage. I've documented 56.8 mpg for a full tank but mostly it's in the 48 - 52 mpg range. The gasser models get reasonalbe mileage but don't compare to the diesels. Overall I think the VW Jetta is a reasonable choice but like you, I think a Toyota or Honda might be more reliable. I have been driving for 52 years and I now own my third and last VW. Good luck with your deliberations.
My GLi Pro SL-2500 Turntable, "Frankencart" And 175 45s




































































