Biologically Active Orexin A & B

Two Novel Hypothalamic Neuropeptides that Regulate Feeding Behavior. Peptide Info: Recently, two novel neuropeptides, both derived from the same precursor by proteolytic processing, termed orexin-A and -B, have been identified within and around the lateral hypothalamus area. These peptides significantly augmented food intake in a dose-dependent manner when a bolus was administered intracerebro- ventricularly. After the 48 hr fast, hypothalamic prepro-orexin mRNA level is up-regulated 2.4-fold as compared with the fed control animals, indicating that a physiological role for these peptides as mediators in the central feedback mechanism that regulates energy balance. The current discovery of orexins and their receptors may provide a novel molecular basis for understanding the role of the lateral hypothalamic areas in the regulation of energy homeostasis.

It will be very interesting to investigate further the possible interplay of orexin with other positive (e.g., Agout-related protein, NPY, galanin, and opiods) and negative (e.g., leptin, melanocortins, CRF, glucagon-like peptide-1, and cholecystokinin) regulators of energy balance both within and outside the central nervous system. Peptide Info: The term orexin comes from "orexins", the Greek word for appetite. Pharmacological intervention directed at the orexin receptors may prove to be an attractive avenue toward the discovery of novel therapeutics for diseases involving the dysregulation of energy homestasis, such as obesity and diabetes mellitus.

Top

Endothelin & Antagonists

Endothelin & Antagonists Click here to see related products Peptide Info: Endothelin is a highly potent vasoconstrictor peptide first isolated from porcine endothelial cell supernatant. Varying amounts of ET are also produced in other cell types such as smooth muscle, neuron, mesangium, melanocyte, parathyroid and aminon. Three structural isoforms of the hormone have been identified (ET-1, ET-2, ET-3) encoded by three distinctive genes expressed independently in the human genome. Individual ET may posses separate physiological or pathophysiological roles in different target tissues.

A metalloprotease, endothelin-converting enzyme, cleaves the Trp21-Val22 (ET-1, ET-2) or Trp21-Ile22 (ET-3) bonds in the longer precursor molecules (Big-ETs) to produce the 21-amino acid bioactive forms. Secretion of ET is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. ETs exert their actions through the activation of at least two receptor subtypes: ET-A receptors, which mediate the proliferative and vasoconstrictive effects, and ET-B receptors, which mediate vasorelaxation. Receptor subtype, ET-A binds ET-1 and ET-2 with much greater affinity than ET-3, while ET-B receptor has similar affinity to all three ET isoforms. Some recent reports also suggest the existance of other receptor subtypes, for example ET-C showing preferential affinity towards ET-3. ETs act to stimulate contraction of many smooth muscle tissues including blood vessels, uterus, bladder, and intestine. ET-1 is the most potent vasoconstrictor peptide yet discovered. Endothelin also shows mitogenic effect on mesangial cells and stimulates mesangial synthesis of extracellular matrix components such as type I, III and IV collagen and laminin. Numerous studies have implicated the ETs in cardiovascular diseases such as hypertension, heart failure, and atherosclerosis. Endothelin levels are elevated in atherosclerosis, congestive cardiac failure and renal insufficiency. Plasma concentrations of IR endothelin are elevated in patients with chronic renal failure. Hypertension may be one of the most important conditions associated with elevated plasma IR endothelin concentrations, although its role remains to be clarified. In healthy humans circulating levels of immunoreactive endothelin-1 are very low, and below the level required for vaso-activity. It has a long duration of action but only 1-2 min of half-life. It is metabolized in the lungs, liver and kidney and is a profound constrictor of the pulmonary, renal, coronary and peripheral circulation. ET may play an important role in homeostatic hemodynamic balance. Endogenous ETs and ET receptor subtypes are present in various endocrine organs. ET appears to act a modulator of secretion of prolactin, gonadotropins, GH and TSH. It is also may act as a neurotransmitter. The amino acid sequences of 21-residue ET-1 from human, porcine, canine, rat, mouse and bovine are identical. Structures of recently isolated snake venom sarafotoxins bear striking resemblance to ETs. Among this family of peptides ET-1 is the most studied compound. Therapeutic potential of endothelins has generated tremendous interest in numerous laboratories around the world. These studies have resulted in the discovery of number of peptides with receptor specific agonist or antagonist properties. Some cyclic peptides containing D-amino acids isolated from fermentation also show very interesting receptor specific antagonist properties. Top

Beta Amyloid Specialists

Alzheimer's vaccine seen as treatment, not cure Peptide Info: Beta Amyloid Specialists (mg to grams) Click here to see related products The aggregation and cerebral deposition of amyloid beta protein (AP), which is a major component of senile plaques in Alzheimer's disease (AD) brains, is believed to be involved in the pathogenesis of AD. The main component of amyloid is made up of about 40 residue peptides that are generated by the proteolytic processing of the amyloid precursor protein. Several researchers have demonstrated that Beta-Amyloid is neurotoxic in-vitro and in-vivo systems. Peptide aggregation state and/or conformation might play a significant role in determining the toxicity of the peptide. Inhibition of Beta-Amyloid aggregation would seem to be a promising strategy for the treatment of AD. Some of the most recent references in this very important area of research are given below. Lit: J Kong, H G Lemaire, A Unterbeck, JM Salboum, CL Masters, KH Grzeschik, G Multhoup, K Beyreuther, B Muller-Hill. Nature 325:733-736; (1987); S Estus, TE Goide, SG Younkin. Ann NY Acad Sci. 674:138-148; (1992); C Hoass, AY Hung, MG Schlossmacher, T Oftersdorf,DB Teplow, DJ Selkoe. Ann NY Acad Sci. 695:109-116; (1993); B Soreghan, J Kosmoski, C Glabe. Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation. Journal of Biological Chemistry 269:28551-28554; (1994); SM Dudek, GVW Johnson. Transglutaminase facilitates the formation of polymers of the b-amyloid peptide. Brain Research 651:129-133; (1994); IV KLNochldn, S Goto. Alzheimer's b-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Letters 345:33-37; (1994); MP Vitek, K Bhottacharya, JM Glendening, E Stopo, H Viossora, R Bucala, K Manogue, A CeraMi. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 91:4766-4770 (1994); C Soto, MC Brones. J Alvarez, NC Inestrosa. Structural determinants of the Alzheimer's amyloid beta-peptide. Journal at Neurochemistry 63:1191-1198; (1994); CL Shen, MC Fitzgerald, RM Murphy. Effect of acid predissolution on fibril size and fibril flexibility of synthetic beta-amyloid peptide. Biophysical Journal 67:1238-1246 (1994); T Tomiyama, S Asono, Y Suwa, T Modta, K Katooka, H Mod. N Endo. Rifampicin prevents the aggregation and neurotoxicity of amyloid beta protein in vitro. Biochemical and Biophysical Research Communications 204:76-83; (1994); LM Maness, WA Banks, MB Podlisny, DJ Selkoe, AJ Kastin. Passage of human amyloid beta-protein 1-40 across the murine blood-brain barrier. Life Sciences 55:1643-1650;(1994) Top

New Cart Peptides

New Cart Peptides Click here to see related products Cocaine and Ampehtamine Regulated Transcript. Leader Sequence MESSRLRLLPVLGALLLLLPLLGAGA Q1EDAELQPRALDIYSAVDDASHEKELPRR QLRAPGAVLQIEALQEVLKKLKSKRI55PIYEKK Y62GQVPMCDAGEQCAV76 RKGARIGKLCDCP RGRSCNSFLLKC L102(Rat)     CART (cocaine- and amphetamine-regulated transcript) was initially identified as mRNA produced primarily in the rat hypothalamus after administration of psychomotor stimulants [1]. The expression of CART mRNA has shown to be regulated by leptin signaling. When systemic leptin or receptors for leptin are inhibited, expression of CART mRNA is suppressed [2]. The translated CART mRNA found in three distinct exons of the CART cDNA results in a 129 amino acid peptide with a predicted leader sequence of 27 amino acids [3]. This hydrophobic leader region corresponds to a signal peptide motif suggesting a post-translational step targeting the CART protein products for cellular secretion. Additional post-translational processing results in the generation of CART(1-52) and CART (55-102) [2]. CART (55-102) has been isolated from the hypothalamus of ovine suggesting in vivo processing at the Lys53-Arg-54 region [4]. Recently, several CART peptides have been shown to inhibit food intake in a dose dependent manner in rats. Thus far, CART (55-102) appears to be the most potent fragment with a conserved secondary structure consisting of three disulfide bridges. The disulfide bridge structure was determined by enzymatic degradation and mass spectroscopy [4] - appetite inhibition is lost when the secondary structure is disrupted by reduction [2]. It was also noted that when rabbit anti-CART(55-102) serum was injected into rats, feeding was significantly increased. When the same serum was allowed to incubate with the anti-CART(55-102) antibody, food intake was no longer inhibited. In addition to CART(55-102), other CART fragments including CART (55-76) and CART (62-76) have also shown to have inhibitory effects on food intake. Icv injection of each fragment reveals dose dependent feeding inhibition in rats [5]. Top

New Leptin Peptides

New Leptin Peptides Click here to see related products

Top

New Nocistatin Peptides

New Nocistatin Peptides Click here to see related products A novel peptide that attenuates pain evoked by nociceptin and prostaglandin E2. The neuropeptide nociceptin, also known as orphanin FQ2, is processed from its precursor prepronociceptin. It induces both hyperalgesia and allodynia when administered by injection through th theca of the spinal cord into the subarachnoid space. Nocistatin 1, a novel biologically active peptide which derived from the nociceptin precursor, blocks nociceptin-induce allodynia and hyperalgesia, and attenuates pain evoked by prostaglandin E2. It is carboxyterminal hexapeptide of nociceptin, which is conserved bovine, heman and murine species, plays opposite rles in pain transmission as nociceptin does. Intrathecal pretreatment with anti-nocistatin antibody decreases the threshold for nociceptin-induced allodynia. The discovery of nocistatin may lead to the design of an novel anlagesic devoid of the addiction and dependence associated with morphine. Top