浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT课件）影响自体活物质的药物 Drugs affecting autacoids

Drugs affecting autacoids

Drugs affecting autacoids

A. Overview Autacoids: local hormones one of the requlator mechanisms in the body

• Autacoids: local hormones • one of the regulatory mechanisms in the body A. Overview

Electrical so neurotransmitter Secreting coll (neuron) Bood Target col Socrotngc hormone (endocrine cem Nontarget ce secretion (no receptors Electrical signal Blood Secreting ce Targot ce (neuron) neurohormone Nontarget secretion (no receptors

neurotrasmitter hormone secretion neurohormone secretion

gap junction secreting arachne旁分泌 autocrine自分泌 juxtacrine接触分泌

gap junction paracrine 旁分泌 autocrine 自分泌 juxtacrine接触分泌

A. Overview Autacoids: Histamine 5-Hydroxytryptamine(serotonin, 5-HT) Lipid-derived autocoids prostaglandins(PGs) Leukotrienes (LTs) Platelet activating factor(PAF) Vasoactive peptides Substance P(SP): Kinins(bradykinin, etc.) Angiotensins(AT); Natriuretic peptides(NP) Vasoactive intestinal peptide (VIP) Endothelins(En Calcitonin gene related peptide(CGRP) Nitric oxide(NO) Adenosine

A. Overview Autacoids: Histamine 5-Hydroxytryptamine (serotonin, 5-HT) Lipid-derived autocoids Prostaglandins (PGs) Leukotrienes (LTs) Platelet activating factor (PAF) Vasoactive peptides Substance P (SP)；Kinins (bradykinin, etc.) Angiotensins (AT)；Natriuretic peptides (NP) Vasoactive intestinal peptide (VIP) Endothelins (ET) Calcitonin gene related peptide (CGRP) Nitric oxide (NO) Adenosine

Phospholipid I(from cell membrane) Corticosteroids>OI@ Bradykinin ) Angiotensin ospnollpase A2 PAF Arachidonic acid Cyclooxygenase Lipid-derived NSAIDs mmm>O autacoids and antagonists related drugs ProstacyclIn(PGL) PGG2 Hydro- peroxidase inhibitors PGE PGF PGH →5 Lipoxygenase 6 Thromboxane A Dipyridamole 5-HPETE Leukotrienes◆…" antagonists

antagonists inhibitors PAF antagonists Lipid-derived autacoids and related drugs

Chemical Arachidonic Acid ESSENTIAL ESTERIFIED ACID and Mechanical COOH Dexamethasone FATTY ACID IN CELL LIPID Cytokines IN DIET e.g, Phospholipids Activation of Growth Factors of Cell Membrane Ph Endotoxin Cyclooxygenase-2 False substrates: e. g see Antinflammatory ^ Figure 26-2 58,11,14 Eicosa e.g., Aspirin and TO coo tetraenoic Acid Indomethacin Dazoxiben cooH CoOH HOOC PGH2 Thromboxane DOH PGG operas Isomerase PGI2 COOH cooH Active HYDROLYSIS PGE 20 PGDHI PGO+ SucrASE metabolites MOXIDATION L, REDUCTION 9a, 11B. PGF2 XIAN 2(0A1w u OX:DATON TION OXIDATION M OXIDATION HYDROLYSA Urinary COOH CoOH O Y PGD-M wo CoOH Prostaglandins(PGs) 11-Dehydro-0 C230m TXB2

Prostaglandins (PGs)

Lipoxygenase +/ATP Arachidonic Acid (cytosolic COOH 5-Lipoxygenase 12-Lipoxygenase (membrane-bound) COOH OOH COOH COOH 12-HETE 12-HPETE 5-HPETE 5-HETE LTA Synthase activity of 5-Lipoxygenase CgHrOH142o03 LTA Hydrolase COOH Leukotriene B4 LTB ChIl Leukotriene A (LTA Leukotriene C4 Synthase cOo cOoH .ShIr H s ,ChUl peptidase GLute Leukotriene E, cys Leukotriene D4 Cys-cl transpeptidase Leukotriene C 9ye-Gy (LTE LTD (LTCA Leukotrienes (LTs): LTB LTC4, LTD4, LTE4

Leukotrienes (LTs): LTB4 ; LTC4 , LTD4 , LTE4

o B Histamine receptor antagonists N N >H1 receptor agonists: CH 2 Histamine(组胺 N一c一cooH 2- methyl histamine(2-甲基组胺) H Betahistine(培他司汀 HistidIne >H2 receptor agonists: Decarboxylase Betazole(培他唑) 2 mpromidine(英普咪定 N N >H3 receptor agonists R(a)- methylhistamine(R(x)-甲基组 CH 胺) H2N-一cH HIstamIne

B. Histamine receptor antagonists ➢H1 receptor agonists: ➢Histamine(组胺) ➢2-methyl histamine(2-甲基组胺) ➢Betahistine (培他司汀) ➢H2 receptor agonists: ➢Betazole (培他唑) ➢Impromidine(英普咪定) ➢H3 receptor agonists: ➢R()-methylhistamine(R ()-甲基组 胺)

3 principal physiological effects (1)it is a mediator of inflammation(swelling) associated with the immune response (2)it is a chemical that stimulates secretion of gastric ac (3) it is a transmitter amine in both the peripheral and the central nervous systems

3 principal physiological effects: (1) it is a mediator of inflammation (swelling) associated with the immune response (2) it is a chemical that stimulates secretion of gastric acid (3) it is a transmitter amine in both the peripheral and the central nervous systems