The induction of phytochelatins (PCs) and their desglycyl peptides (both are referred to as class III metallothionein [CIIIMT]) by exposure to various metals (Ag+, As3+, As5+, CdZ+, Cuz+, Ca3+, HgZ+, ln3+, Ni2+, PbZ+, Pd2+, Se4+, and ZnZ+) and the metal composition in the ClllMTs were investigated in root cultures of Rubia tinctorum L. All of these metal species induced PCs to various degrees when analyzed by the postcolumn derivatization highperformance liquid chromatography method. The desglycyl peptides of PCs often were also present. However, only Ag, Cd, and Cu were bound to the ClllMTs that they induced when analyzed by the high-performance liquid chromatography-inductively coupled plasma-atomic emission spectrometry method. Cu was also bound to the ClllMTs induced by Ag+, As3+, and Cd2+. After Ag+ exposure, an Fe peak that may be of Fe-CIIIMT was also observed. However, most of the metal species studied were not bound to the ClllMTs that they induced. ~~~

The effects of synthetic rat adrenomedullin (rAM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma. on receptor binding and CAMP generation were studied in cultured rat vascular smooth muscle cells (VSMC). A binding study using ["51]rAM revealed the presence of a single class of high-affinity (& 1.3 x lo-* M) binding sites for rAM m VSMC. The apparent K, of rat calcitonin gene-related peptide (rCGRP) was 3 x lo-' M. Affinity labeling of VSMC membranes with ["'I]rAM revealed two distinct labeled bands with apparent molecular weights of 120 and 70 kDa, both of which were abolished by excess unlabeled rAM or rCGRP. rAM stimulated CAMP formation with an approximate EC,, of lo-* M, the effect of which was additive with isoproterenol, but not with rCGRP. The rAM-induced CAMP response was unaffected by propranalol. indomethacin, or quinacrine, but inhibited by a CGRP receptor antagonist, human CGRP[8-371. These data suggest that VSMC possesses specific AM receptors functionally coupled to adenylate cyclase with which CGRP interacts.

Human adrenomedullin (hAM), a potent vasodilatory peptide originally identified in pheochromocytoma, has been shown to be present in various human tissues and circulate in human plasma. We measured plasma concentrations of immunoreactive hAM in patients with sepsis who had been admitted to intensive care unit (ICU). Plasma hAM concentrations in 12 septic patients upon entering the ICU were extremely elevated (107 +/- 139 fmol/ml: mean +/- SD) compared to those of 16 age-matched normal subjects (7.9 +/- 3 fmol/mL). Among 10 patients with normal renal function, plasma hAM levels either decreased or increased during the hospital course; the former group survived and the latter group succumbed. Two patients with acute renal failure had markedly elevated plasma hAM levels during the early course, which declined rapidly during the recovery course. High performance liquid chromatography of plasma extracts from one patient with acute renal failure revealed a single major component of immunoreactive hAM coeluting with authentic hAM (1-52) during acute and recovery phase. Plasma hAM concentration showed positive correlations with heart rate, right atrial pressure, and serum creatinine concentration, but not with other hemodynamic variables. These data suggest that a marked increase in circulating hAM in sepsis may be caused by its decreased clearance and/or its enhanced synthesis by multiple organ dysfunction, and that increased endogenous hAM may be involved in the mechanism of cardiovascular abnormalities associated with sepsis.

The application of pressure to solid iodine forces the molecules in the crystal to approach each other until intermolecular distances become comparable to the bond length of iodine; at this point, the molecules lose their identity and are essentially dissociated. According to room-temperature X-ray diffraction studies, this process involves direct dissociation of iodine molecules at about 21 GPa, whereas spectroscopic observations have identified intermediate molecular phases at pressures ranging from 15 to 30 GPa. Here we present quasi-hydrostatic powder X-ray diffraction measurements that clearly reveal an intermediate phase during the pressure-induced dissociation of solid iodine. We find that, similar to the behaviour seen in uranium, the structure of this intermediate phase is incommensurately modulated, with the nearest interatomic distances continuously distributed over the range 2.86-3.11 A. The shortest of these interatomic distances falls between the bond length of iodine in the molecular crystal (2.75 A) and the nearest interatomic distance in the fully dissociated monatomic crystal (2.89 A), implying that the intermediate phase is a transient state during molecular dissociation. We expect that further measurements at different temperatures will help to elucidate the origin and stability of the incommensurate structure, which might lead to a better understanding of the molecular-level mechanism of the pressure-induced dissociation seen here and in the molecular crystals of hydrogen, oxygen and nitrogen.