response or cAMP accumulation was inhibited by pertussis toxin. In conclusion, the present study demonstrates that EDG7, a new member of the EDG family of G-protein-coupled receptors, is a specific LPA receptor that shows distinct properties from known cloned LPA receptors in ligand specificities, Ca 2؉ response, modulation of adenylyl cyclase, and MAP kinase activation.

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P < .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

No abstract

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by Fc⑀RI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A 1 , PS-PLA 1 , stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of Fc⑀RI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA 1 , in which an active serine residue (Ser 166 ) was replaced with an alanine residue did not show such activity. sPLA 2 -IIA, another secretory PLA 2 that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA 1 significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA 1 . Finally, heparin, which has affinity for PS-PLA 1 , completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA 1 may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.