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30 Cards in this Set
- Front
- Back
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What are kininogens and where are they found?
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Acidic glycoproteins and precursors of kinins.
Found in blood plasma, GIT fluids and lymph. |
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Distribution of low v. high molecular weight kininogens?
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LMW can cross blood vessel wall and distribute in tissues.
HMW remain primarily in blood plasma |
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Chemical structure of Bradykinin?
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Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
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Chemical structure of Kallidin (Lysylbradykinin)?
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Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
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Half life and metabolism of kinins?
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very short half-life ~15 seconds.
Principal catabolizing enzyme is the angiotensin converting enzyme (ACE). |
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Ligand potency order for the B1 kinin receptor?
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[des-Arg9]bradykinin > [Tyr(Me8)]bradykinin > bradykinin
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Ligand potency order for the B2 kinin receptor?
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[Tyr(Me8)]bradykinin > bradykinin > [des-Arg9]bradykinin
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Location of B1 kinin receptor?
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mostly in vascular smooth muscle
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Location of B2 kinin receptor?
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widespread G-protein coupled receptors
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Post-receptor mechanisms for kinin receptors?
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Ca2+ mobilization, Cl- transport, synthesis of NO, activation of PLC, PLA2 and adenylyl cyclase
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What is the effect of kinins on vessels?
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~10-fold as potent vasodilators as histamine - in vascular beds in the heart, kidney, intestine, skeletal muscle and liver.
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Mechanism of the effect of kinins on vessels?
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Release of NO and EDRF from endothelial/epithelial cells (similar to histamine), and activate PLA2 (PGE2 and PGI2).
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Are the hypotensive effects of kinins long or short lasting? Why?
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Short due to the rapid degradation of kinins.
Also counteracted by reflex tachycardia, increase of myocardial contractility and cardiac output. |
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What is the effect of kinins on endothelial cells?
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Contraction. May = edema.
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What is the effect of kinins on endocrine/exocrine glands?
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could regulate the tone of salivary and pancreatic ducts, and hence GI motility
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What is the effect of kinins on nutrient transport?
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regulates the transepithelial transport of water, electrolytes, glucose and amino acids in the kidneys and GIT
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Role of kinins in inflammation?
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Inflammatory lesions are associated with production of high local concentrations of kinins. Injected kinins mimic inflammation: produce redness, local heat, swelling and pain.
Bradykinin produces the wheal-and-flare response (as does histamine) |
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What is the effect of kinins on sensory nerves?
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kinins elicit pain by stimulation of nociceptive (algesic) afferents in skin and viscera
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What is the effect of kinins on airways?
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Bradykinin has little direct effect on the bronchial smooth muscle but causes bronchoconstriction, secondary to release of histamine
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Clinical use and structure of kinin agonists?
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Peptide analogues.
No therapeutic use. Used in research. |
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Properites and clinical use of B1 kinin receptor inhibitors?
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Peptides only. Very short half-life, low efficiency.
No therapeutic use. Used in research as inhibitors of inflammatory effects of kinins. |
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Properites and clinical use of B2 kinin receptor inhibitors?
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1st and 2nd generations: peptides, low efficiency.
3rd generation WIN 64338 and FR 173657, block bradykinin-induced bronchoconstriction. No therapeutic use. Used in research. |
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What's Aprotinin?
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protease inhibitor, inhibits synthesis of kinins and production of inflammatory mediators.
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Clinical use of Aprotinin?
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Used for treatment of Systemic Inflammatory Response Syndrome (SIRS).
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How do Aspirin and indomethacin work?
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COX2 inhibitors, block effects of kinins mediated by prostaglandins and prostacyclin = inflammation inhibitors
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Mechanism of inflammation?
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Kinins -> PLA2 -> Arachidonic acid metabolism -> Inflammatory mediators
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What are Captopril and enalapril?
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ACE inhibitors, delay degradation of kinins and potentiate their hypotonic effect.
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What's icatibant? Uses?
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B2 receptor antagonist.
Successful Phase I and Phase II clinical trials for hereditary angioedema. |
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What's Hereditary angioedema?
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Debilitating and potentially life-threatening genetic disease. Pts have unpredictable recurring swelling attacks in the hands, feet, face, larynx, and abdomen. Poss due to elevated blood levels of bradykinin, and higher expression of kinin receptor
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What are the detrimental effects of kinin?
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Mediate pain and itching
Mediate inflammation Potent vasodilators: angioedema |
