Endogenous peptides and proteins include well characterized families of neuropeptide transmitters, neuropeptide modulators, hormones, and fragments of functional proteins, which are essential in many biological processes. The peptides exert potent biological actions in virtually all systems in the body (see figure for examples). Pharmaceutical products which mimic the effects of endogenous peptide ligands are call peptidomimetics. Some examples of peptidomimetics and their corresponding endogenous ligand include desmopressin – vasopressin, octreotide – somatostatin, and insulin glargine – insulin. Drugs which block the receptors for endogenous peptide ligands can be peptide or non-peptide molecules. Examples include naloxone (opioid receptors), aprepitant (substance P receptors), and losartan (angiotensin II type 1). Pharmacology of proteins and peptides Pharmacology of proteins and peptides Pharmacology of Proteins and Peptides Gastrointestinal peptides The gastrointestinal hormones constitute a group of hormones secreted by enteroendocrine cells in the stomach, pancreas, and small intestine. This group of hormones regulate various functions of the digestive organs. Some of the major families are listed below.Gastrin–cholecystokinin family: gastrin (gastrin-34,"big gastrin"; gastrin-17, "little gastrin"; gastrin-14, "minigastrin") and cholecystokinin (CCK-58, CCK-33, CCK-22 and CCK-8)Secretin family: secretin, glucagon, vasoactive intestinal peptide and gastric inhibitory peptideSomatostatin family: SRIF-28 (= somatostatin), SRIF-14Substance PGhrelin, a growth hormone secretagogue synthesised by endocrine cells in the stomach, stimulates gastrointestinal motility like motilin agonistsGastrointestinal peptides, their site(s) of expression and major functions. Hormone or peptideMajor tissue locations in the gutPrincipal known actionsBombesin: neuromedin B, gastrin releasing peptideThroughout the gut and pancreasStimulate release of cholecystokinin (CCK) and gastrinCalcitonin gene-related peptide: α-CGRP, β-CGRPEnteric nervesUnclearChromogranin ANeuroendocrine cellsSecretory proteinEnkephalinsStomach, duodenumOpiate-like actionsEnteroglucagonSmall intestine, pancreasInhibits insulin secretionGalaninEnteric nervesUnclearGhrelinStomachStimulates appetite, increases gastric emptyingGlucagon-like peptide 1Pancreas, ileumIncreases insulin secretionGlucagon-like peptide 2Ileum, colonEnterocyte-specific growth hormoneGrowth factorsThroughout the gutCell proliferation and differentiationGrowth hormone-releasing hormoneSmall intestineUnclearLeptinStomachAppetite controlMotilinThroughout the gutIncreases gastric emptying and small bowel motilityNeuropeptide YEnteric nervesRegulation of intestinal blood flowNeurotensinIleumAffects gut motility; increases jejunal and ileal fluid secretionPancreatic polypeptidePancreasInhibits pancreatic and biliary secretionPeptide YYColonInhibits food intakeSomatostatin: SRIF-28, SRIF-14Stomach, pancreasInhibits secretion and action of many hormonesSubstance PEnteric nervesUnclearTrefoil peptides: trefoil factor 1, trefoil factor 2, trefoil factor 3Stomach, intestineMucosal protection and repair Overview of gastrointestinal peptides in health and disease Synthesis, secretion, and regulation of gastrointestinal peptides Neuropeptides Neuropeptides are small proteinaceous cell-cell signaling molecules produced and released by neurons. They differ from peptide hormones in that they are secreted from neurons and act locally on neighbouring neurons, whereas peptide hormones are secreted in to the blood by neuroendocrine cells and act at distant sites. Neuropeptides are the most diverse class of signaling molecules in the brain, and are involved in a broad range of brain functions, including analgesia, reproduction, learning and memory, reward, food intake and more. Characteristics relevant to neuropeptide function are 1) their secretion is through a 'regulated' route, 2) they are not recycled once secreted and 3) they may be modified in the extracellular space by peptidases which can either inactivate their biological activity or conversely, increase target binding affinity.Neuropeptides often co-exist with other neurotransmitters in defined cell populations, but are contained in separate storage vesicles. Neuropeptides are held within large dense-core vesicles (LDCVs) throughout the cell body, whereas neurotransmitters are contained in small vesicles located at synapses.In humans there are ~90 genes encoding neuropeptide precursors, which are processed to ~100 bioactive neuropeptides. The Neuropeptide Database Endocrine peptides Endocrine peptides are the proteinaceous subset of the hormones produced by the glands of the endocrine system. The major endocrine glands include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus, gastrointestinal tract and adrenal glands. Endocrine hormones regulate a vast array of bodily functions including metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood.The table below provides details of the endocrine glands, the hormones they secrete and some of the principal effects of the hormones. Non-peptide hormones are shown in italics for clarity.Endocrine organSecreted hormone(s)Effect(s)Hypothalamusthyroid-releasing hormone (TRH)stimulates release of TSH from anterior pituitaryHypothalamusdopamineinhibits prolactin release from anterior pituitaryHypothalamusgrowth hormone-releasing hormone (GHRH)stimulates GH release from anterior pituitaryHypothalamussomatostatininhibits release of GH and TSH from anterior pituitaryHypothalamusgonadotropin-releasing hormone (GnRH)stimulates release of FSH and LH from anterior pituitaryHypothalamuscorticotrophin-releasing hormone (CRH)stimulates ACTH release from anterior pituitaryHypothalamusvasopressinincreases water permeability in distal convoluted tubule: increases blood volumePineal glandmelatoninregulates circadian rhythmPituitary gland- anteriorgrowth hormone (GH)-somatotrophsstimulates growth and cell proliferation; stimulates hepatic insulin-like growth factor 1 releasePituitary gland- anteriorthyroid-stimulating hormone (TSH)- thyrotrophsstimulates thyroxine (T4) and triiodothyronine (T3) synthesis and release from thyroid gland; stimulates iodine uptake by thyroid glandPituitary gland- anterioradrenocorticotropic hormone (ACTH)- corticotrophsstimulates corticosteroid (glucocorticoid and mineralocorticoid) and androgen synthesis and release from adrenocortical cellsPituitary gland- anteriorbeta endorphin- corticotrophsinhibits pain sensationPituitary gland- anteriorfollicle-stimulating hormone (FSH)- gonadotrophsstimulates ovarian follicle maturation in females; stimulates maturation of seminiferous tubules, spermatogenesis and production of androgen-binding protein in malesPituitary gland- anteriorluteinizing hormone (LH)- gonadotrophsstimulates ovulation and formation of corpus luteum in females; stimulates testosterone synthesis from Leydig cells (interstitial cells) in malesPituitary gland- anteriorprolactin (PRL)- lactotrophsstimulates milk synthesis and release from mammary glands; mediates sexual gratificationPituitary gland- anteriormelanocyte-stimulating hormone (MSH)- melanotrophsstimulates melanin synthesis and release from melanocytes in hair and skinPituitary gland- posterioroxytocin- magnocellular neurosecretory cellsstimulates uterine contraction during labour; stimulates the letdown reflex in nursing mothersPituitary gland- posteriorvasopressin (ADH or AVP)- parvocellular neurosecretory neuronsincreases water permeability in distal convoluted tubule: increases blood volumeThyroid glandT3-thyroid epithelial cellsmore potent form of thyroid hormone- increases basal metabolic rate; stimulates protein synthesisThyroid glandT4- thyroid epithelial cellspro-hormone for T3- same effectsThyroid glandcalcitonin- parafollicular cellsreduces blood calcium; stimulates bone formationGI tract-stomachgastrin- G cellsstimulates secretion of gastric acid by parietal cellsGI tract-stomachghrelin- P/D1 cellsincreases appetiteGI tract-stomachneuropeptide Y (NPY)increases food intakeGI tract-stomachsomatostatin- D cellssuppresses release of gastrin, cholecystokinin (CCK), secretin, motilin, vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), enteroglucagon; slows gastric emptying; reduces smooth muscle contraction and blood flow in intestineGI tract-stomachhistamine- ECL cellsstimulates gastric acid secretionGI tract-stomachendothelin- X cellsregulates smooth muscle contraction in stomachGI tract-duodenumsecretin- S cellsregulates secretion of bicarbonate from liver, pancreas and Brunner's gland (duodenum); enhances effects of CCK, stops gastric juice productionGI tract-duodenumcholecystokinin (CCK)- I cellspromotes release of digestive enzymes from pancreas and release of bile from the gall bladder; hunger suppressantGI tract-liverinsulin-like growth factor 1 (somatomedin, IGF)- hepatocytesinsulin-like effects; regulates growth and developmentGI tract-liverangiotensinogen- hepatocytesvasoconstriction; stimulates release of aldosterone from adrenal cortexGI tract-liverangiotensin- hepatocytesvasoconstriction; stimulates release of aldosterone from adrenal cortexGI tract-liverthrombopoietin (THPO)- hepatocytesstimulates megakaryocytes to produce platelets in the bone marrowGI tract-liverhepcidin- hepatocytesinhibits intestinal iron absorption and iron release by macrophagesGI tract-pancreasinsulin- β islet cellsstimulates glucose absorption from blood to skeletal muscles and fat tissue; promotes fat storage; inhibits hepatic glucose productionGI tract-pancreasglucagon- α islet cellsincreases blood glucose level; stimulates glycogenolysis and gluconeogenesis in liverGI tract-pancreassomatostatin- δ islet cellsinhibits insulin and glucagon release; inhibits exocrine secretion from pancreasGI tract-pancreaspancreatic polypeptide- PP cellsmodulates hepatic glycogen levels and gastrointestinal secretions; auto-regulates pancreatic secretionKidneyrenin- juxtaglomerular cellsstimulates the renin-angiotensin system by producing angiotensin I from angiotensinogenKidneyerythropoietin- extraglomerular mesangial cellsstimulates erythrocyte productionKidneycalcitrol (active form of vitamin D3)stimulates absorption of calcium and phosphate from GI tract and kidneys; inhibits release of parathyroid hormoneKidneythrombopoietinstimulates megakaryocytes to produce platelets in the bone marrowAdrenal glands- cortexglucocorticoids- zona fasciculata and zona reticularis cellsstimulate gluconeogenesis; stimulates fat breakdown in adipose tissue; inhibit protein synthesis and glucose uptake in muscle and adipose tissue; immunosuppressive; anti-inflammatoryAdrenal glands- cortexmineralocorticoids- zona glomerulosa cellsstimulate active sodium reabsorption and passive water reabsorption in kidneys (increasing blood volume and pressure); stimulate renal potassium and H+ excretionAdrenal glands- cortexandrogens: DHEA and testosterone- Zona fasciculata and Zona reticularis cellsmasculising effects in females; in males, effects are insignificant compared to those elicited by testicular androgensAdrenal glands- medullaadrenaline- chromaffin cellspromotes mechanisms underlying the fight-or-flight response e.g. boosting oxygen and glucose supplies to the brain and muscles, increasing heart rate and stroke volume, increasing hepatic glycogen catalysis, and suppressing non-emergency bodily-processesAdrenal glands- medullanoradrenaline- chromaffin cellspromotes mechanisms underlying the fight-or-flight response e.g. boosting oxygen and glucose supplies to the brain and muscles, increasing heart rate and stroke volume, increasing hepatic glycogen catalysisAdrenal glands- medulladopamine- chromaffin cellsincreases heart rate and blood pressureAdrenal glands- medullaenkephalin- chromaffin cellsregulates painReproductive organs- testesandrogens- Leydig cellsanabolic effects; virulizingReproductive organs- testesestradiol- sertoli cellsprevents apoptosis of germ cellsReproductive organs- testesinhibin- sertoli cellsinhibits FSH productionReproductive organs- ovarian follicle and corpus luteumprogesterone- granulosa cells, theca cellssupports pregnancyReproductive organs- ovarian follicle and corpus luteumandrostendione- theca cellsmetabolic precursor of both testosterone and estroneReproductive organs- ovarian follicle and corpus luteumestrogens (mainly estradiol)- granulosa cellspromotes development of secondary female sex characteristics; stimulates endometrial growthReproductive organs- ovarian follicle and corpus luteuminhibin- granulosa cellsinhibits FSH productionReproductive organs- pregnant placentaprogesteronesupports pregnancy; inhibits onset of labour and lactation; supports fetal mineralo- and glucocorticosteroid productionReproductive organs- pregnant placentaestrogenseffects on mother similar to ovarian follicle-derived estrogenReproductive organs- pregnant placentahuman chorionic gonadotropin (hCG)- syncytiotrophoblastpromotes maintenance of the corpus luteum at the beginning of pregnancy; suppresses the immune response to the developing embryoReproductive organs- pregnant placentahuman placental lactogen-syncytiotrophoblastincreases insulin and IGF-1 production; increases insulin resistance and carbohydrate intoleranceReproductive organs- pregnant placentainhibin- fetal trophoblastsinhibits FSH productionReproductive organs- pregnant uterusprolactin (PRL)- decidual cellsstimulates milk production in mammary glandsReproductive organs- pregnant uterusrelaxin- decidual cellsrelaxes the ligaments in the pelvis and softens and widens the cervixParathyroid glandparathyroid hormone (PTH)- parathyroid chief cellsincreases the concentration of ionic calcium (Ca2+) in the blood; decreases serum phosphate; promotes renal activation of vitamin DSkincalcidiol (25-hydroxyvitamin D, inactive form of vitamin D3) Heartatrial-natriuretic peptide (ANP)- cardiac myocytesreduces blood pressureHeartbrain natriuretic peptide (BNP)- cardiac myocytesreduces blood pressureSkeletal musclemyokines Adipose tissueleptin- adipocytesappetite suppressant; increases metabolic rateAdipose tissueestrogens (mainly estrone)- adipocytes This article was published on 2025-01-28
