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SUMMARYRelaxation of smooth muscle cells induced by activation of fi-adrenoceptors was investigated in intact and skinned muscles of the guinea-pig mesenteric artery.1. In concentrations over 10-7 M, isoprenaline reduced the resting tone of intact preparations and also the amplitude of K contractions. When Ca was applied after previous superfusion with Ca-free solution, the amount of Ca accumulated into storage sites was increased by isoprenaline in polarized and depolarized ([K]0 128 mM) muscles. The amount of Ca stored increased even further when procaine and isoprenaline were applied simultaneously during store loading.2. Isoprenaline increased the concentration of cyclic AMP as determined by radioimmunoassay. Application of isoprenaline at a concentration of 10-7 M increased cyclic AMP from 2-2 + 0 3 to 2-8 + 0-6 p-mole/mg wet weight and at 10-6 M increased it to 4-5 + 08 p-mole/mg wet weight after 5 min incubation (n = 4).3. Application of cyclic AMP (3 x 10-6 M) with cyclic AMP-dependent protein kinase (50 jg/ml.) had no effect on the pCa-tension relationship in the skinned muscles. However, an increased concentration of cyclic AMP (> 10-5 M) suppressed the Ca-induced concentration only in the presence of protein kinase. This protein kinase (50 ,tg/ml.) alone had no effect on the Ca-induced contraction.4. In skinned fibres, the Ca store could be loaded by applying low concentrations of Ca. If cyclic AMP (3 x 10-6 M) with protein kinase (50 jug/ml.) was applied during the loading procedure, the amount of Ca accumulated by the store increased if the loading solution contained 10-6 M-Ca applied for 2 min or less, but if the loading solution was applied for 3 min, or if higher Ca concentrations were used, the presence of cyclic AMP with protein kinase decreased the store size, suggesting that a Cainduced Ca-release mechanism was also being activated.5. In skinned muscles, accumulation of Ca into the store site in the presence of cyclic AMP (3 x 10-6 M) with protein kinase (50 gg/ml.) was further accelerated by simultaneous applications of procaine (5 mM), as here the Ca-induced Ca-release mechanism was suppressed.6. These results indicate that activation of f-adrenoceptors by isoprenaline increases the amount of cyclic AMP in the intact muscles, and leads to an increase in Ca accumulation into the store site. In the skinned muscles, the Ca-induced

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To clarify the cellular origin and characteristics of malignant mixed müllerian tumor (MMMT), the authors investigated two cell lines (designated as FU‐MMT‐1 and FU‐MMT‐2) established from two patients with heterologous MMMT of the uterus. Both cell lines propagated continuously for 83 and 55 serial passages over 1.5 years, respectively. Morphologically, FU‐MMT‐2 was a mixture of carcinoma cells and sarcoma cells with predominance of carcinoma cells; FU‐MMT‐1 only had a sarcomatous element with distinct rhabdomyoblastic differentiation. Immunocytochemically, the sarcoma cells of each cell line expressed, not only myogenic and mesenchymal antigens (desmin, myoglobin, and vimentin), but also epithelial antigens, including epithelial membrane antigen and keratin. The carcinoma cells in FU‐MMT‐2 were positive for the epithelial antigens and vimentin and negative for desmin and myoglobin. Both lines had abnormal karyotypes; the modal chromosome numbers of FU‐MMT‐1 and FU‐MMT‐2 were 47 and 80, respectively. In addition, FU‐MMT‐1 had trisomy 8, and FU‐MMT‐2 had complex structural abnormalities. When transplanted into nude mice, FU‐MMT‐1 reproduced and maintained the characteristics of the original tumor. These cell lines and xenografts appear to provide a useful system for studying the biologic behavior, cytogenetic features, and histogenesis of MMMT. In conclusion, the presence of epithelial antigens in the sarcomatous and carcinomatous elements seemed to support the hypothesis that both elements are derived from a common stem cell.