<p> Biochemistry Second Messengers</p><p>Vitamin A: a. Gt b. Transducin activates cGMP phosphodiesterase activity to decrease circulating cGMP and induce light sensation</p><p>Epinephrine a. Depends on receptor</p><p> α1: Gq</p><p> α2: Gi</p><p> β1: Gs</p><p> β2: Gs b. β receptor stimulation causes increased cAMP activity causes insulin decrease, and cortisol/glucagon increase c. α2 receptor stimulation causes the opposing effects due to lowered cAMP levels</p><p>Insulin: a. Insulin receptor tyrosine kinase (IRTK) b. Induces IRS-1, IRS-2, PLC, and SHC</p><p>IGF-1: a. IGF-1 receptor tyrosine kinase (similar to IRTK) b. Induces cartilage, bone, and muscle growth</p><p>Prolactin/GH: a. JAK receptor b. Binding causes downstream activation of STAT and gene transcription</p><p>T3: a. Nuclear T3 receptor that heterodimerizes with RXR receptor b. Causes upregulation of gene transcription leading to increased production </p><p> of UCP, Na+/K+ ATPase, 1-adrenergic receptor, and GH.</p><p>1,25 D signaling: a. Nuclear VDR receptor heterodimerizes with RXR receptor b. Increases IL-6 release, ODF release, and osteocalcin release in bone; increases apical Ca2+ channels, Ca2+ binding protein, and basolateral Ca2+/ATPase in the intestine Glucocorticoid: a. Nuclear receptor (GR) homodimer b. Glucocorticoid binds GR which homodimerizes to induce gene transcription</p><p>Mineralocorticoid: a. Nuclear receptor (MR) homodimer b. Mineralocorticoid binds MR which homodimerizes to induce gene transcription</p><p>Glucagon: a. Gs b. Increased cAMP and a subsequent increase in gluconeogenesis</p><p>Vasopressin: a. Gs b. Increases PKA to combine with aquaporin-2 and increase water reabsorption in the distal nephron</p><p>GHRH: a. Gs b. Increases cAMP → PKA → CREB → gene transcription for GH synthesis and release</p><p>LH: a. Gs b. cAMP activity induces P-450scc to start androgen synthesis</p><p>Thyroid stimulating hormone: a. Gs b. TSH binds to the thyroid follicular cell causing an increase in cAMP </p><p> activity  PKA  endocytosis of thyroglobulin/MIT/DIT/T4/T3 aggregate.</p><p>PTH signaling: a. Gs</p><p> b. Increases osteoblastic cAMP  renal excretion of cAMP, PO4.  IL-6 release  osteoclastic resorption of bone mineral  ODF release  multinucleate osteoclast differentiation Calcitonin signaling: a. Gs</p><p> b. Increases osteoclastic cAMP  decreases osteoclast activity</p><p>Angiotensin II: a. Gs b. Activates cholesterol esterase and P-450scc in the zona fasciculata/reticularis</p><p>ANP inhibition:</p><p> a. Gs (via 1 adrenergic receptor) b. PKA inhibits release of ANP</p><p>GHIH: a. Gi b. Decreases cAMP and blocks GH synthesis and release</p><p>Dopamine effect on prolactin: a. Gi b. Inhibits posterior pituitary release of prolactin </p><p>GnRH: a. Gq 2+ b. Increases PKC, CaM dependent kinase, and Ca to induce LH, FSH release</p><p>ACTH: a. Gq b. Activates cholesterol esterase and P-450scc in the zona glomerulosa as well as inducing StAR transcription (via cAMP) and maximal activity (via PKA)</p><p>ANP activation:</p><p> a. Gq (via 1 adrenergic receptor) b. PKC induces release of ANP</p><p>Oxytocin: a. Gq 2+ b. Increased Ca causes increased function in both mammary and uterine tissue Angiotensin II action: a. Gq 2+ b. Increases intracellular Ca which activates CaM kinase. CaM kinase and PKC phosphorylate enzymes to increase the steroidogenic pathway, increasing aldosterone levels and Na+ reabsorption.</p><p>PTH release: 2+ a. Inhibition by Ca sensitive Gq b. High Ca2+ inhibits PTH release by increasing intracellular calcium via IP3/DAG/Ca2+. (PTH is released when intracellular calcium is low)</p><p>ANP action: a. Guanylyl cyclase b. Increases intracellular cGMP  PKG, which phosphorylates Ca2+ channels in the membrane and decreases Ca2+ influx (the opposite of the angiotensin II pathway)</p>