Purinergic compounds can decrease neural activity peripherally and centrally [l-4]. The spontaneous firing rates of cerebellar Purkinje neurons fall precipitously after adenosine or its analogs are applied locally [5]. The amplitude of hippocampal excitatory postsynaptic potential (EPSP) responses is depressed by adenosine and its analogs [S, 61. The depression of EPSP amplitudes of pyramidal n...

In order to assess the potential importance of different cellular binding sites for the adverse effects of aminoglycosides (i.e. oto- and nephrotoxicity) the binding of neomycin and calcium to phospholipids and other anionic cell constituents was assayed in vitro. Phospholipids demonstrated binding affinities that strongly favored neomycin (Km, 10 to 100 microM) over calcium (Km, 300 to 1,120 m...

The o-nitrophenyl group at position 4 of dihydropyridine of nifedipine analogues was replaced with 2-alkylthio-1-benzyl-5-imidazolyl substituent. Starting from dihydroxyacetone 2-alkythio-1-benzyl- 5-formyl imidazole (3) was first synthesized which was subsequently used in synthesizing symmetrical (5a-f) and asymmetrical (6a,b) dihydropyridines. Primarily pharmacological studies of the title co...

Wood creosote, a mixture of phenolic compounds, suppresses in vitro contractions of rat intestine. To identify a compound in wood creosote able to inhibit intestinal motility, we screened its constituent phenolic compounds and found 4-ethylguaiacol (4-EG) as an active compound. It suppressed the spontaneous phasic (IC50 = 513 +/- 48 mumol/l) as well as spasmogenic-agent-induced tonic longitudin...

We were able to purify two distinct sodium pump inhibitors to homogeneity from human urine based on [3H]ouabain-displacing activity from intact human erythrocytes. The polar and less polar compounds were eluted off the C18 reverse-phase column with 18% and 31% acetonitrile, respectively. The polar compound cross-reacted very weakly with specific antidigoxin antibody and lacked a characteristic ...

TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasonin...

I47 Tsien’s group classified these channels as ‘N, ‘T, In the 1960s the research groups of Fleckenstein and Godfraind defined ‘calcium antagonists’ as agents which blocked the entry of calcium into cells via voltage-dependent calcium channels. In a literature search we found 74 compounds in various stages of clinical or preclinical development classed as ‘calcium antagonists’. Since the initial...

The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that...

lactose), and the formation of a " skin " (due to drying of protein on the surface, and not peculiar to milk). These changes are not of great importance as regards the infant. The next group consists of changes not appreciable by the ordinary observers, namely the precipitation of calcium, and alterations in the organic phosphorus compounds. The former renders the caseinogen less coagulable in ...