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adrenergic stimulating agents such as isoproterenol result in bronchodilatation associated with a rise in intracellular C-AMP, whereas beta blocking agents or cholinergic stimulation leads to broncho-constriction associated with a fall in intracellular C-AMP. There is increased evidence that asthma is a systemic disorder associated with partial beta adrenergic blockade since (1) asthmatic patients exhibit a reduced generalized metabolic response to epinephrine, (2) the peripheral lymphocytes show a decreased antigenic inactivation by cate-cholamines, and (3) there is a reduction in the rise of lymphocytic C-AMP in response to isoproterenol in blood from asthmatics as compared with controls (10).
The possibility of involvement of prostaglandins in asthma stems from the observation that PGE, and PGE, relax human bronchiolar smooth muscle in vitro, while PGF, contracts these muscles and inhibits the bronchodilating effect of isoproterenol. Arthritis
Intradermal injection of complete Freund's adjuvant produces a serve polyarthritis which is prevented or inhibited by subcutaneous administration of PGE, and PGE, but not by PGA or PGF, compounds (11). It has been suggested that one mechanism by which PGE, might alleviate experimental arthritis is immunologic, involving inhibition of sensitized lymphocytic migration into the affected joints by increasing lymphocytic C-AMP. Drugs that increase the latter compound have been shown to decrease lymphocytemediated cytolysis of target cells (11). Paradoxically PGE, and PGE, in smaller doses appear to produce experimental arthritis and are capable of evoking such signs of inflammation as pain, swelling, heat, and redness. At present, the role of PGE's in inflammation in both experimental and human rheumatoid arthritis is unknown. Immediate Hypersensitivity
One model of immediate hypersensitivity is antigen-induced histamine release from IgE antibody-sensitized basophils and from the lung, a reaction which is inhibited by catecholamines and C-AMP, PGE, and PGE, but not by PGF. The effect of catecholamines is on beta adrenergic receptors, since their inhibition of histamine release can be blocked by propranolol, whereas no such inhibition occurs with PGE, (11). In addition, catecholamine inhibition of histamine release is associated with a rise in leukocyte C-AMP
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