secreted by one cell & acts upon adjacent cells or surrounding extracellular matrix [ecm]...
TRANSCRIPT
PARACRINE MEDIATORS
AUTOCRINE MEDIATORS
Secreted by one cell & acts upon adjacent cells or surrounding extracellular matrix [ECM]
Secreted from a cell and acts on the same cell
Paracrine Autocrine Mediators Chemically they are classified into
MONOAMINESHistamineSerotonin …etc
PEPTIDESContractants Angiotensin EndothelinNPYVasopressin
Relaxants Kinines ANPTachykinins [SP]VIP ….etc
EICOSANOIDSProstaglandinsProstacyclinesThromboxane A2
Leukotrienes …etc
PURINESATP / ADPAdenosine
NO OTHERSCytokinesChemokineGrowth Factors….etc.
MONOAMINE (HISTAMINE )
Storage Sites
Highest amounts in mast cells
Basophils Skin Lung Intestinal mucosa Stomach Brain
Storage and release:
Histamine is usually found in storage granules as complex with sulfated polysacharides, heparin and released (locally) by:
a) immunologicl Mechanism (During Allergic Reaction (see Fig 56-5)
b) Tissue injury Mast cell degranulation
c) Chemical and physical Conditions ( see table 51-2)
Chemical and Physical Agents that Release HistaminePhysical Agents Chemical Agents
Mechanical trauma, Radiant energy, Thermal energy
Chymotrypsin, Compound 48/80, Detergents, Dextran, DMSO (dimethyl- sulfoxide), Morphine and other Opiods, Pentamidine , Polymyxin B, Polyvinyl pyrrolidine, Propamidine, eserpine, Surface active agents, Stilbamidine, Toxins, Tubocurarine, venoms, X-ray contrast media
SYNTHESIS & INACTIVATIONTION
H 2
H 1
H 3
H
istamine Mediator
NeurotransmitterCNSANS
H 3
+
+
+
H 1
-ve presynaptic autoregulation
ReceptorType
Major Tissue Locations Major Biologic Effects
H1smooth muscle, endothelial cells
acute allergic responses
H2gastric parietal
cellssecretion of gastric acid
H3central nervous
systemmodulating neurotransmission
H4
mast cells, eosinophils, T
cellsregulating immune responses
Histamine receptors
Histamine receptors antagonists
What is the physiological Antagonist of Histamine?
First generation Diphenhydramin, Promethazine etc
(Sedating and Pass Blood Brain Barriers)
Clinical uses :Antinausia and VomitingInsomniaCough Motion sicknessAllergy
H1 antagonists
Second generation.Loratadine
Non-sedatingClinical uses Allergic conditions Allergic rhinitis ConjunctivitisUrticaria
H1 antagonists
Ranitidine
Inhibitor of gastric acid secretion Used in the treatment of peptic ulcers
H2 antagonists
BETAHISTINE (Betaserc)
Used in treatment of vertigo in middle ear
H3 antagonists
EICOSANOIDS (PROSTAGLANDINS)
INHIBITORS OF EICOSANOIDS
Phospholipids Phospholipase A2
Arachidonic Acid
Prostaglandins PGE2, PGD2, PGF2
Thromboxane (TXA2)
Prostacyclin (PGI2)
COX1 & COX2
LeukotrienesLTA4, B4, D4, C4 (Zafirlukast as Antagonist)
Lipoxygenase
Drugs
NSAIDs
Corticosteroids
Zileuton
ACTIONS
Vascular smooth muscles:
Potent vasoconstrictor.
PGE2 and PGI2
Thromboxane A2
Potent vasodilators.
Blood:
PGE2 and PGI2
inhibit platelet aggregation
TXA2 a potent
inducer of platelet aggregation.
One of the chemical mediators in inflammatory reactions.
Inflammation:
-PGF2
-LTs and thromboxane are potent bronchoconstrictors in man → allergic bronchospasm .
Bronchial smooth muscle:
-PGE2 cause dilatation.
Uterine smooth muscle:
PGE2 and PGF2 → Menstruation/ Dysmenorrhea/ Labor contractions
- PGE2 and PGF2
GIT smooth muscle:
GITmotility
GIT secretions:
PGE2 , PGE1 PGI2
↓acid and pepsinogen secretion .
mucin, water and bicarbonate & Blood flow.
Thus, it is cytoprotective
PGE2 and PGI2 increase renal blood flow and diuresis.
Kideny
Central and peripheral nervous systems
Fever: PGE1 and PGE2 increase body temperature.
CLINICAL USES OF PGS ANALOGS
Carboprost
PGF2α ( analog)
1) Abortifacient:
Trigger abortion in first trimester.
2) For postpartum haemorrhage
vasoconstriction
(PGF2α analog )
eye drops in open angle glaucoma.
↓ IOP by enhancing outflow of the aqueous humar.
Latanoprost
Alprostadil
(PGE1analog)
1 -Injected in corpus cavernosum of the penis for some forms of male impotence.
2 -In congenital heart anomalies
to keep the patent ductus arteriosus until
surgery .
Misoprostol
(PGE1 analog)
Peptic ulcer
Clinical Uses:
Oxytocis agents: (e.g.: Dinoprostone PGE2)
Asthma: Leukotrien antagonists (Zafirleukast; Montelukast); Zileuton
Impotance: Alprostadil PGE2
Glaucoma: Latanoprost PGF2
Anti-inflammatory and RA (NSAIDs) Antiplatelet action (Aspirin) Peptic Ulcer (Minoprostol PGE1)(Cytotec)
Thank you & Good Luck