1 We investigated the e ects of [Nle 4 ,D-Phe 7 ]a-melanocyte-stimulating hormone (NDP-MSH), adrenocorticotropin-(1 ± 24) (ACTH-(1 ± 24)) and g 2 -MSH, three melanocortins with di erent agonist selectivity for the ®ve cloned melanocortin receptors, on blood pressure and heart rate in conscious, freely moving rats following intravenous administration. 2 As was previously found by other investigators as well as by us, g 2 -MSH, a peptide suggested to be an agonist with selectivity for the melanocortin MC 3 receptor, caused a dose-dependent, short lasting pressor response in combination with a tachycardia. Despite the fact that NDP-MSH is a potent agonist of various melanocortin receptor subtypes, among which the melanocortin MC 3 receptor, it did not a ect blood pressure or heart rate, when administered i.v. in doses of up to 1000 nmol kg 71 . 3 ACTH-(1 ± 24) caused a dose-dependent decrease in blood pressure in combination with a dosedependent increase in heart rate in a dose-range from 15 to 500 nmol kg 71 . The cardiovascular e ects of ACTH-(1 ± 24) were independent of the presence of the adrenals. 4 Pretreatment with ACTH-(1 ± 24) caused a pronounced, dose-dependent parallel shift to the right of the dose-response curve for the pressor and tachycardiac e ects of g 2 -MSH. The antagonistic e ect of ACTH-(1 ± 24) was already apparent following a dose of this peptide as low as 10 nmol kg 71 , which when given alone had no intrinsic hypotensive activity. 5 These results form further support for the notion that it is not via activation of one of the as yet cloned melanocortin receptors that g-MSH-like peptides increase blood pressure and heart rate. The cardiovascular e ects of ACTH-(1 ± 24) seem not to be mediated by the adrenal melanocortin MC 2 receptors, for which ACTH-(1 ± 24) is a selective agonist, or by adrenal catecholamines. 6 There appears to be a functional antagonism between ACTH-(1 ± 24) and g 2 -MSH, two melanocortins derived from a common precursor, with respect to their e ect on blood pressure and heart rate. Whether this antagonism plays a (patho)physiological role remains to be shown.

To study the derivation of tumor cells of malignant fibrous histiocytomas (MFH), their phenotypical marker profile was investigated and compared with those of malignant histiocytosis (MH) and of different types of soft tissue tumors (STT). The presence of the following markers was investigated: on paraffin sections, alpha-1-antichymotrypsin (ACT); on frozen sections antigens associated with lymphocytes, macrophages and fibroblasts, the enzymes acid phosphatase, nonspecific esterase, and beta-glucuronidase; and, on isolated and cultured cells, the receptors for EA-gamma and complement. Furthermore, the capacity to phagocytose sensitized erythrocytes and carbon particles was studied in vitro. MFH tumor cells and a part of other types of STT shared the expression of ACT and lysosomal enzymes with MH. They differed, however, from MH by the absence of monocyte/macrophage-associated antigens and by the expression of fibroblast-associated antigens, which property they had in common with other STT. MFH tumor cells were not able to form rosettes or to phagocytose Ig-sensitized erythrocytes, but they showed phagocytosis of carbon particles. The results strongly indicate that MFH tumor cells originate from (primitive) fixed mesenchymal cells and are not related to monocyte-derived histiocytes.

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