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Somatostatin-14 (SS) si gnificantly increased inositol-l,4,5-trisphosphate (IP3) accumulation in rat hypothalamic, striatal, frontoparietal cortical and hippocarapal slices. However, this stimulation of IP 3 accumulation by SS was highest in the frontoparietal cortex and hippocampus. The effect was already significant with 0.01/~M in the frontoparietal cortex (P < 0.05) and hippocampus (P < 0.05) and the maximal accumulation was evident with 0.1/tM SS, in all areas studied. A concentration of 1/~M SS, lacked this effect in hypothalamus and striatum. SS rapidly increased IP 3 accumulation in all brain areas studied. This effect was maximal at 15 s of incubation and decreased subsequently. At 60 s incubation, levels were still elevated in frontoparietal cortex and hippocampus but had returned to basal values in hypothalamus and striatum. Somatostatin-28 (SS-28) and the SS analogues, D-Trp8-D-Cys 14 and SMS 201-995, also significantly stimulated IP~ accumulation although the effect of SMS 201-995 was greater than that of SS in the striatum in comparison with controls (P < 0.001 and P < 0.01, respectively). These results suggest that SS action at the hypothalamus, striatum, frontoparietal cortex and hippocampus is mediated at least in part by the accumulation of IP 3, which may initiate intracellular processes responsible for some biological SS effects.

The effects of a commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1248) and two individual PCB congeners were evaluated on rat renal proximal tubule culture cell viability and internucleosomal DNA fragmentation (DNA ladder) characteristic of apoptosis. Treatment with Aroclor 1248 caused the loss of cell viability and promoted apoptosis in a concentration- and time-dependent manner. The two PCB congeners assessed can also induce apoptosis. However, the extent of apoptosis generated was greater for the non-ortho-substituted planar congener (3,3',4,4-tetrachlorobiphenyl) than for the di-ortho-substituted nonplanar congener (2,2',4,4',5,5'-hexachlorobiphenyl). This correlated with the loss of cell viability since the planar compound is much more cytotoxic. The results suggest a different molecular mechanism in the induction of apoptosis by planar or nonplanar PCB congeners.

The influence of lindane upon phosphatidylinositol hydrolysis in rat brain cortex slices has been investigated using anion-exchange chromatography in order to separate the water-soluble inositol metabolites. Acetylcholine, noradrenaline, and lindane induce the accumulation of myo-[2-3H]inositol as the water-soluble inositol metabolites. However, the cholinergic muscarinic antagonist atropine inhibited the stimulatory response of carbachol, but practically unmodified the effect that lindane has on inositol phosphate production. Also, prazosin anti-alpha 1 adrenoreceptors blocked noradrenaline-induced phosphoinositide hydrolysis, but had no effect on lindane-induced increase of inositol phosphate levels. The results suggest that lindane does not exert a general effect on the receptor-stimulated formation of inositol phosphates by both muscarinic and alpha 1-adrenergic agonists.