Melanotropin Receptors and Signal Transduction
Mac E. Hadley in The Melanotropic Peptides, 2018
Peptide hormones are physiologically active molecules important in a variety of endocrine, neuroregulatory, and other cellular processes. Structurally, linear and cyclic peptides are composed of an ordered, covalent sequence of amino acids which ultimately defines specific topological and, in a few well-studied examples, conformational features essential to their molecular action.16 Functionally, the biological activity of many peptide hormones on their target cells has been shown to involve interaction with a plasma-membrane-localized, complex regulatory enzyme system including: (1) high-affinity, hormone-specific receptors; (2) guanyl nucleotide-binding proteins; (3) monovalent and divalent metal-binding proteins; and (4) adenylate cyclase. In addition, the phospholipid milieu of the plasma membrane may also provide a regulatory role in biological signal transduction by coordinating the activities of the functional components of this enzyme system. The molecular basis of such peptide-receptor binding and subsequent signal transduction processes are elaborated further in Table
Effects of Stress on Physiological Conditions in the Oral Cavity
Eli Ilana in Oral Psychophysiology, 2020
Recently, newly-discovered neuropharmacological substances have been reported as possible mediators of the interrelationship between stress and periodontal disease.87 Apparently, peptide hormones, such as substance P and bombesin affect not only the neurological system but also such behavior as drinking, eating, sexual drive, pain, and pleasure.88 These aspects of mood can, therefore, influence behaviors such as diet (nutrition) or change in oral hygiene habits. Peptide hormones can also induce changes in lymphocyte cells which lead to the production of other hormones (i.e., growth hormones) and vasoactive intestine peptides. As lymphocytes are a common inflammatory cell of the periodontium, mood can presumably affect the periodontal condition in this manner.87
The heart in hypertension
H. Gavras in The Year in Hypertension 2004, 2004
BACKGROUND. Peptide hormones and growth factors are known to act by binding to cell surface receptors and subsequently activate intracellular mediators of signal transduction. Over the last three decades evidence has accumulated to indicate that at least some peptide hormones and growth factors also bind and act in the cellular interior, either after internalization by target cells or retention in their cells of synthesis. Several years ago the authors' laboratory proposed the term intracrine for such intracellularly acting peptide hormones irrespective of whether their binding/action followed internalization or occurred in the cell that sythesized them. In fact, many intracrines act in both fashions (Table 2.1).
The role of peptide-based therapeutics in oncotherapy
Published in Journal of Drug Targeting, 2021
Selin Seda Timur, R. Neslihan Gürsoy
A significant portion of clinically approved peptides consist of peptide hormones used in cancer therapy. A typical case is Gonadotropin-releasing hormone (GnRH) agonists (i.e.buserelin and leuprolide) as well as antagonists (i.e. abarelix and cetrorelix) which are utilised in prostate cancer treatment. Another similar group is somatostatin analogs, which are used either alone or in combination with radionuclide in peptide receptor radionuclide therapy (PRRT) during cancer treatment [41]. The success of the clinically approved peptide hormones has caused several researchers to divert their focus towards the use of peptide analogs for targeted cancer therapy. In the case of Gonadotropin-releasing hormone (GnRH), a decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) naturally produced to control reproductive functions in the body, the receptor -(LHRH receptor) is overexpressed in different cancers including breast, prostate and ovarian cancer, thus providing an opportunity for receptor mediated-tumour targeting for therapy and diagnosis [42,43]. GnRH, also known as luteinizing hormone-releasing hormone (LHRH), was utilised in cancer therapy as targeting moiety in form of conjugates with anticancer drugs, polymers, or drug delivery systems such as liposomes, dendrimers, micelles, and silica nanoparticles [42,44]. Antineoplastic agents such as doxorubicin, cisplatin, melphalan as well as imaging agents like DOTA were conjugated to GnRH to enhance conventional cancer diagnosis and therapy [42,45].
Subcutaneous catabolism of peptide therapeutics: bioanalytical approaches and ADME considerations
Published in Xenobiotica, 2022
Simone Esposito, Laura Orsatti, Vincenzo Pucci
Therapeutic peptides represent a unique niche that occupies a well-established chemical space between small molecules and large biologics. Peptide-based drugs account for a small yet relevant portion of the pharmaceutical market, with worldwide sales of more than $70 billion in 2019 and further growth expected in the coming years (Muttenthaler et al. 2021). Therapeutic peptides drug discovery started in the early twentieth century with natural human hormones like insulin and gonadotropin-releasing hormone. However, the identification of other peptide hormones with potential therapeutic properties and the significant technological innovations in the fields of synthesis, analysis, and purification of recombinant biologics and in structural biology have considerably accelerated the development of therapeutic peptide drugs. Notably, over 60 peptides have been approved in the last two decades in the United States, Europe and Japan, and more than 150 are currently undergoing clinical trials, covering a wide range of therapeutic areas (Wang et al. 2022). Although new indications continue to emerge, the main therapeutic areas are metabolic disease and oncology, followed by infectious disease, inflammation, cardiovascular, respiratory disease, and urology.
Pancreatic atrophy and exocrine insufficiency associate with the presence of diabetes in chronic pancreatitis patients, but additional mediators are operative
Published in Scandinavian Journal of Gastroenterology, 2021
Søren Schou Olesen, Rasmus Hagn-Meincke, Asbjørn Mohr Drewes, Emilie Steinkohl, Jens Brøndum Frøkjaer
We confirmed that pancreatic atrophy (indicated by reduced pancreatic volume) was independently associated with the presence of PPDM. This is in keeping with past studies and reflects the conventional view of PPDM as a result of beta cell loss and insulin deficiency [25]. However, in addition to insulin, a number of other peptide hormones are secreted from the pancreatic islet cells including glucagon (alpha cells) and pancreatic polypeptide (delta cells).These hormones are important for the maintenance of glucose homeostasis and regulate muscle and liver insulin sensitivity. Hence, islet cell destruction resulting from CP does not only lead to insulin deficiency, but also a lack of counter regulatory hormones, which results in a ‘brittle diabetes’ that can be difficult to treat and are associated with high risk of hypoglycemic episodes and hyperglycemic crisis [1,4].