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By Jill Ruiz Carreon Arginine vasopressin (AVP) Argipressin “Pressor” effect is secondary significance 9 amino acids Produced in hypothalamus Released from posterior pituitary (pars nervosa) to the blood Stimulates water retention in the kidneys Less water excreted in urine Regulates and balances water in blood Released into the brain by neurons of the hypothalamo-hypophyseal tract Suprachaismatic nuclei (SCN) ◦ Regulation of circadian rhythms ◦ Circadian clock genes – transcribed into mRNA proteins Role in species-typical patterns of social behavior Hypotension Increases vasoconstriction Arterial BP Compensatory / Regulatory However, also seen in patients with heart failure ◦ Too many AVP receptors / AVP secretion ◦ Sympathetic and renin-angiotensin system activation in heart failure override hypothalamic control of AVP release ◦ May contribute to the increase in systemic vascular resistance as well as in renal retention of fluid Minimal pressor effects in humans Regulation of extracellular fluid Conserve body water by reducing urine output ADH binds to aquaporins in the plasma membranes of the collecting duct epithelial cells ◦ Transports solute-free water through tubular cells ◦ Back into blood ◦ Decreases plasma osmolarity and increases urine osmolarity Work with ADH to maintain water metabolism By sensors in the hypothalamus reacting to the ccn of particles in your blood ◦ Na+, K+, Cl-, CO2, etc ◦ Unbalanced / sensors tell kidneys to store or release water to maintain a healthy range Regulate body’s sense of thirst Specialized membrane channel proteins Made up of single peptide chain consisting of about 270 aa Facilitate water transport across cell membranes At least 7 expressed in kidneys ◦ AQP 1, 2, 3, 4, 6, 7, 11 Role in short- & long-term regulation of water balance and pathophysiology of water balance disorders Aquaporin Group Localization in Kidney AQP 1 APM/BLM of proximal tubules and descending thin limbs AQP 2 APM/VES of principal cells of collecting ducts AQP 3 BLM of collecting ducts AQP 4 BLM of medullary collecting ducts AQP 6 Cortex, Medulla AQP 11 Proximal tubule (Intracellular) AQP: Aquaporin, APM: Apical membrane, BLM: Basolateral membrane, VES: Vesicles Cloned as an ADH-regulated water channel of CD Basal state: AQP2 stored in intracellular vesicular compartment With ADH stimulation, it moves quickly to apical membrane where it acts as water channel for the ccn of urine ADH acts at V2 receptors in BLM of CD principal cells Protein-coding gene Subfamily of G-protein coupled receptors ◦ AVPR1B, V2R and OXT receptors Mediates: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Vasoconstriction Antidiuresis ACTH release Cell contraction and proliferation Platelet aggregation Release of coagulation factor Glycogenolysis By G proteins that stimulate a phosphatidylinositol-calcium second messenger system AVPR2 gene provides for production of this protein Located on Chromosome Xq28 ADH + V2 Receptor = trigger chemical reactions for body’s water balance control SIADH Symptoms: ◦ Headache, Nausea, Vomiting Associated with: ◦ Leukemia, lymphoma, lung / pancreatic / bladder / brain cancers, systemic cancers that produce ADH, MS, Epilepsy, Acute intermittent porphyria, TB, dehydration, brain trauma, and surgery Nephrogenic diabetes insipidus ◦ very dilute urine ◦ Symptoms: excessive urination (polyuria), extreme thirst (polydipsia) May be due to compulsive water drinking or low blood serum osmolality Central diabetes insipidus ◦ in production of ADH by hypothalamus or realease of ADH from pituitary gland ◦ Symptoms: excessive urination (polyuria), extreme thirst (polydipsia), often tired since sleep interrupted by urination urges, clear, odorless and has low ccn of particles in urine ◦ Lead to severe dehydration “Antidiuretic Hormone (ADH) Test” http://www.healthline.com/health/adh#Purpose3 “Aquaporins: The renal channels” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813137/ “AVPR1A arginine vasopressin receptor 1A [Homo sapiens (human)]” https://www.ncbi.nlm.nih.gov/gene/552 “AVPR1A Gene (Protein Coding)” https://ghr.nlm.nih.gov/gene/AVPR2#resources “AVPR2 Gene” https://ghr.nlm.nih.gov/gene/AVPR2#resources “Definition of Antidiuretic Hormone (ADH)” http://www.medicinenet.com/script/main/art.asp?articlekey=7000 http://images.slideplayer.com/29/9441578/slides/slide_13.jpg Human Physiology, McGraw Hill “Vasopressin” http://www.healthline.com/health/adh#Purpose3 “Vasopressin (Antidiuretic Hormone)” http://www.cvphysiology.com/Blood%20Pressure/BP016.htm