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
Regulation of Cell Functions
Enrique Pimentel in Handbook of Growth Factors, 2017
In contrast to the classical hormones, the peptide growth factors (usually called in an abbreviated manner “growth factors”) are not necessarily synthesized in specialized endocrine organs but are produced and secreted by cells from a wide variety of tissues, and their target cells are frequently located not far from the site of release (paracrine response). Even the cell producing a growth factor may in some cases (when it is endowed of the specific receptor) respond to the factor (autocrine response).4-8 Certain growth factors remain anchored to the cell membrane.9 The distinction between peptide hormones and growth factors may be a subtle one, however. Many growth factors, or proteolytic products of growth factors, circulate in the blood and may act at sites far away from the place of their secretion or may display specific regulatory functions. Growth factors, or substances with growth factor-like activities, have been found not only in vertebrates but also in invertebrates and even in plants, where they are represented by biologically active agents called cytokinins.
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.
Novel oxytocin receptor antagonists for tocolysis: a systematic review and meta-analysis of the available data on the efficacy, safety, and tolerability of retosiban
Published in Current Medical Research and Opinion, 2021
Greg Marchand, Richard Blumrick, Alexandra D. Ruuska, Kelly Ware, Ahmed Taher Masoud, Alexa King, Stacy Ruther, Giovanna Brazil, Kaitlynne Cieminski, Nicolas Calteux, Hollie Ulibarri, Katelyn Sainz
As a result of all these complications, a constant search for effective medications to stop PTL is an important goal of obstetrics. The treatment of PTL relies on the inhibition of uterine contractions so labor can ideally be delayed for at least 48 h, a period sufficient to allow the pregnant woman to be transferred to a center specialized in the management of preterm deliveries, to administer corticosteroids to reduce neonatal organ immaturity, and to administer magnesium for neuroprotection32. Currently available tocolytic agents include nonsteroidal anti-inflammatory drugs, calcium channel blockers, β-agonists, and—outside the US—oxytocin antagonists33,34. Oxytocin is an important target in treatment options. It is a peptide hormone secreted from the hypothalamus and released by the posterior pituitary gland. It has many physiological functions; however, it is best known for its role in uterine contractions during parturition35. Thus, oxytocin receptor antagonism theoretically inhibits uterine contractions.