Nimodipine's interactions with other drugs: I. Ethanol

Adult mice (Binghamton Heterogeneous stock) received different doses of ethanol (0.5, 1.0, or 2.0 g/kg) administered alone or in combination with the voltage-sensitive calcium channel antagonist, nimodipine (Bay e 9736). Both 20 and 60 minutes later, sensitivity to ethanol was assessed in terms of rotorod activity and changes in rectal temperatures. Nimodipine (5 mg/kg) alone did not alter rectal temperature or motor coordination, but at both observation periods nimodipine potentiated the hypothermia induced by the highest dose of alcohol (2.0 g/kg) and exaggerated alcohol-induced motor incoordination at all doses. The present set of results indicates that the inhibition of voltage-dependent calcium channels can exaggerate ethanol-induced effects.     

Bryophyte interactions with other plants

Bryophytes live in microhabitats determined by the physical environment, usually modified by the vascular plant vegetation, and seemingly in 'ecological isolation' from other plants.
However, bryophytes are involved in a variety of competitive, parasitic, symbiotic, mutualistic and as yet unspecifiable interactions with vascular plants, algae, fungi, lichens, cyanobactcria and autotrophic and heterotrophic bacteria. In only very few cases have these interactions been analysed functionally. Yet, such information may be essential for a better understanding of (1) such aspects of bryophyte ecology as mineral nutrition, carbon economy, herbivory, and growth and development of the gametophyte, and (2) the ecological role of bryophytes in terrestrial ecosystems.     

Carbachol interactions with nonsteroidal anti-inflammatory drugs

The inhibition of cyclooxygenase enzymes by nonsteroidal anti-inflammatory drugs (NSAIDs) does not completely explain the antinociceptive efficacy of these agents. It is known that cholinergic agonists are antinociceptive, and this study evaluates the interactions between carbachol and some NSAIDs. Antinociceptive activity was evaluated in mice by the acetic acid writhing test. Dose-response curves were constructed for NSAIDs and carbachol, administered either intraperitoneally (i.p.) or intrathecally (i.t.). The interactions of carbachol with NSAIDs were evaluated by isobolographic analysis after the simultaneous administration of fixed proportions of carbachol with each NSAID. All of the drugs were more potent after spinal than after systemic administration. The combinations of NSAIDs and carbachol administered i.p. were supra-additive; however, the i.t. combinations were only additive. Isobolographic analysis of the coadministration of NSAIDs and carbachol and the fact that atropine antagonized the synergistic effect suggest that carbachol may strongly modulate the antinociceptive activity of NSAIDs; thus, central cholinergic modulation would be an additional mechanism for the antinociceptive action of NSAIDs, unrelated to prostaglandin biosynthesis inhibition.     

Study of DNA interactions with steroidal and nonsteroidal estrogen-platinum (II)-based anticancer drugs

The interactions of the steroidal and nonsteroidal estrogen-platinum (Pt) (II)-based anticancer drugs 16beta-hydroxymethyl-16alpha-[8-(2-pyridin-2-yl-ethylamino)-3,6-dioxaoctyl]-1,3,5(10)-estratrien-3,17betadiol dichloroplatinum (II) (JPM-39), 4-[6-(2'-pyridylethylamino)-butyloxy)-phenyl]-7-methoxy-2,2-dimethyl-3-phenyl-chroman dichloroplatinum (II) (ATG-99), and 1-[(2-aminoethyl)amino]-9,10,10-tris(4-hydroxyphenyl)-9-decene dichloroplatinum (II) (GEB-28) with calf-thymus DNA in vitro using constant DNA concentration and various drug levels were studied. Fourier transform infrared (FTIR) and circular dichroism (CD) were studied with calf-thymus DNA in vitro using constant DNA concentration and various drug levels. FTIR, UV-visible, and CD spectroscopic methods were used to characterize the drug binding mode, the binding constant, and structural variations of DNA in aqueous solution. Spectroscopic evidence showed that the various Pt-based drugs bind indirectly to the major and minor grooves of DNA duplex with some degree of drug-phosphate interaction. The overall binding constants for JPM-39, GEB-28, and ATG-99 are K(JPM-39) = 4.2 (+/-0.75) x 10(3) M(-1), K(GEB-28) = 3.4 (+/-0.65) x 10(3) M(-1), and K(ATG-99) = 2.1 (+/-0.45) x 10(3) M(-1). DNA aggregation occurs at high drug concentration, while DNA remains in the B-family structure.     

Chromium(III) interactions with nucleotides. II

New derivatives were obtained from Cr(urea)₆Cl₃· 3H₂O in an ethyl acetate medium of chromium(III) with uracil, uridine, 5′UMP, 5′CMP, 5′GMP and 5′IMP. The new derivatives were characterized by elemental analysis, electronic and infrared spectroscopy and thermal analysis. These derivatives proved to be outer sphere complexes, in which the nucleotide, the nucleoside or the base interacts with the starting complex through intramolecular hydrogen bonding.Cr(XMP)(OH)·3H₂O (XMP: 5′UMP, 5′CMP, 5′GMP and 5′IMP) complexes were obtained by hydrolysis of the above derivatives of the nucleotides. In these reactions there is a total substitution of the urea molecules. The derivatives obtained by hydrolysis were characterized in solid state by electronic and infrared spectroscopy. These results provide more insight into the biological role of chromium.     

Pig platelet tropomyosin: interactions with the other thin-filament proteins

Pig platelet tropomyosin exhibits many of the functional activities of skeletal tropomyosin. At low ionic strength it forms end-to-end aggregates similar to those formed by skeletal tropomyosins. It forms a 1:1 complex with muscle troponin or with a troponin I-pig brain calmodulin complex, as well as a 1:6 association with platelet filamentous actin. Electron microscopy of paracrystals shows that the troponin binding site is slightly C-terminal of the unique cysteine, corresponding to position 190 of the rabbit skeletal alpha-tropomyosin sequence. The effect of a complex comprising platelet actin and tropomyosin on the ATPase activity of rabbit skeletal muscle myosin subfragment-1 was similar to that displayed by its skeletal muscle counterpart. Platelet tropomyosin decreased the activity by roughly half in a calcium-independent manner. Addition of troponin to the actin-tropomyosin in the absence of calcium results in further inhibition and allows the full activity of the complex to be restored by Ca2+. These results differ from those obtained by C?té & Smillie for horse platelet tropomyosin and this may reflect the different isomeric nature of pig platelet tropomyosin. These results suggest that the functional properties of non-muscle tropomyosins may differ when comparisons are made between proteins isolated from the same type of cell but in different species. Differences in self-association and actin-binding properties may be finely graded between different isoforms.     

Ternary interactions of spermine with DNA: 4''-epiadriamycin and other DNA: anthracycline complexes.

The recently developed anthracycline 4'-epiadriamycin, an anti-cancer drug with improved activity, differs from adriamycin by inversion of the stereochemistry at the 4'-position. We have cocrystallized 4'-epiadriamycin with the DNA hexamer d(CGATCG) and solved the structure to 1.5 A resolution using x-ray crystallography. One drug molecule binds at each d(CG) step of the hexamer duplex. The anthracycline sugar binds in the minor groove. A feature of this complex which distinguishes it from the earlier DNA:adriamycin complex is a direct hydrogen bond from the 4'-hydroxyl group of the anthracycline sugar to the adenine N3 on the floor of the DNA minor groove. This hydrogen bond results directly from inversion of the stereochemistry at the 4'-position. Spermine molecules bind in the major groove of this complex. In anthracycline complexes with d(CGATCG) a spermine molecule binds to a continuous hydrophobic zone formed by the 5-methyl and C6 of a thymidine, C5 and C6 of a cytidine and the chromophore of the anthracycline. This report discusses three anthracycline complexes with d(CGATCG) in which the spermine molecules have different conformations yet form extensive van der Waals contacts with the same hydrophobic zone. Our results suggest that these hydrophobic interactions of spermine are DNA sequence specific and provide insight into the question of whether DNA:spermine complexes are delocalized and dynamic or site-specific and static.     

Theoretical calculations of base-base interactions in nucleic acids: II. Stacking interactions in polynucleotides.

Base-base interactions were computed for single- and double stranded poly,ucleotides, for all possible base sequences. In each case, both right and left stacking arrangements are energetically possible. The preference of one over the other depends upon the base-sequence and the orientation of the bases with respect to helix-axis. Inverted stacking arrangement is also energetically possible for both single- and double-stranded polynucleotides. Finally, interacting energies of a regular duplex and the alternative structures were compared. It was found that the type II model is energetically more favourable than the rest.     

Protein-protein interactions of hCsl4p with other human exosome subunits.

The exosome is a complex of 3'-->5' exoribonucleases, which functions in a variety of cellular processes, all requiring the processing or degradation of RNA. We demonstrate that the two human proteins hCsl4p and hRrp42p, which have been identified on the basis of their sequence homology with Saccharomyces cerevisiae proteins, are associated with the human exosome. By mammalian two-hybrid and GST pull-down assays, we show that the hCsl4p protein interacts directly with two other exosome proteins, hRrp42p and hRrp46p. Mutants of hCsl4p that fail to interact with either hRrp42p or hRrp46p are also not able to associate with exosome complexes in vivo. These results indicate that the association of hCsl4p with the exosome is mediated by protein-protein interactions with hRrp42p and hRrp46p.