Studies on Calcium-activated, Unsaturated Fatty acid-dependent Guanylate Cyclase in Membranes.

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Cyclic GMP in an intact cell system was reported to increase by various biologically active compounds as neurotransmitters and hormones. Guanylate Cyclase in cell-free system can not be stimurated by agents increasing cyclic GMP contents. A mechanism of receptor-operated enhancement of cyclic GMP formation has been unclear. Recently we described the Ca^<2+>-activated, unsaturated fatty acid-dependent Guanylate Cyclase (CF-Guanylate Cyclase) in synaptic plasma membranes. This enzyme system plays possibly an important functional role in transmembrane-signal-transduction.The stimulatory substances of the cyclase, Ca^<2+> and unsaturated fatty acid which are librated intramembranously on receptor-stimulation are proposed to be a mediator probably participating in a receptor-guanylate cyclase coupling. In this study, we examined purification procedures and some properties of CF-Guanylate Cyclase.The mechanism of the activation of this cyclase by Ca^<2+> and fatty acid was partly clarified. In chromatographies of this enzyme, a factor, we named it CF-Guanylate Cyclase modulator (GCM) was separated from the enzyme preparation, which significantly modulated the activation by fatty acids. The factor was purified by several steps of chromatographies and estimated to be approx. 37K. The properties of the factor is now under investigating.