164 WALDMAN AND MURAD the cell type, physiological state, and the protocol used for enzyme assay. Thus, in some tissues such as the normal adult liver (190, 187) or platelets(124, 23), guanylate cyclase is predominantly soluble. In other tissues, such as regenerating liver (194, 130), fetal liver (194), hepatomas and renal tumor (130, 50, 51, 65), intestinal mucosa(191, 276, 56), and retinal rod outer segments (200, 91, 92, 129, 68, 90), the enzyme is predominantly particulate. Furthermore, there are cell types, including C6 rat glioma, B103 rat neuroblastoma(306), and sea urchin sperm (112, 108, 277, 132, 133), which appear to possess particulate guanylate cyclase exclusively. There appears to be no correlation between the subcellular localization of the enzyme and phylogeny. Soluble guanylate cyclase is the predominant form observed in the procaryote E. coil (237), while the particulate enzyme is the predominant form in Sendai virus (195) and the eucaryotic protozoans, such as Tetrahymena pyriformis (175, 202, 203) and Paramecium tetraurelia(297, 298, 196). It should be noted that, in the case of Sendai virus, it remains unclear whether particulate guanylate cyclase originates as a product of the viral or host genome(195). The apparent relative distribution of guanylate cyclase between the soluble and particulate compartments is profoundly affected in most cells by the presence of detergents in the homogenizing medium or enzyme assay. Particulate guanylate cyclase activity can be increased as much as 3-to 12-fold with detergents, while much less activation of the soluble enzyme(30 to 100%) occurs. This has been observed with preparations from most tissues and cell cultures including kidney, liver, parotid, uterus, cerebellum, heart, sea urchin sperm, skeletal muscle, cerebral cortex, blood vessels, hepatomas, neuroblastomas, gliomas, and pheochromocytomas(190, 191, 306, 112, 108, 277, 132, 337, 334, 206, 336, 38, 269, 314, 315, 289, 254, 250, 342, 172, 145, 193, 100, 346, 98, 326, 214, 267). Increased activity in the presence of detergents correlates closely with release of enzyme from membranes into the soluble phase and has been attributed to the particulate guanylate cyclase being latent (190, 108, 277, 132, 337, 334, 206, 336, 38, 269, 314, 315, 289, 172, 145, 193, 100, 346, 98, 326, 214, 267). Whether increases in activity reflect solubilization of enzyme molecules normally sequestered in the membrane and unavailable to substrate or represent activation of enzyme is discussed in a later section. The alterations in physical and biochemical properties of both soluble and particulate guanylate cyclases exposed to detergents are also the subject of a later section.

Studies of the subcellular distribution of guanylate cyclase have indicated that there are at least more than two forms of this enzyme in most cell types. Particulate guanylate cyclase has been associated with plasmalemma, endoplasmic reticulum, Golgi (191, 192), and nuclear membranes(78) when these organelles were purified from homogenates of rat liver. Similarly, enzyme