Interaction between endogenous opioids, cholinergic and adrenergic mechanisms during vagally-induced gastrin release in rats

Endogenous opioids are present in neurons of the vagus and the intrinsic nervous system and they are colocalized with gastrin in antral G-cells. This raises the possibility that endogenous opioids modulate gastrin release. Stimulation of both cervical vagi (10V, 5Hz, 5ms) elicited an increase of arterial plasma gastrin levels at intragastric pH7 or pH2. The response at pH2 was 30% of that at luminal pH7. Atropine reduced vagally stimulated gastrin levels substantially. At luminal pH2 the small residual noncholinergic response was mediated neither by adrenergic mechanisms nor by endogenous opioids. At luminal pH 7 adrenergic blockade with phentolamine and propranolol reduced vagally stimulated gastrin by 60%. In the presence of atropine adrenergic blockade elicited only a small inhibitory effect suggesting that vagal activation of adrenergic mechanisms depends on atropine-sensitive cholinergic pathways. Blockade of opiate receptors by naloxone had no effect on vagal gastrin release, however, the noncholinergic gastrin response was reduced significantly by naloxone, suggesting that cholinergic mechanisms normally restrain activation of endogenous opioids during vagal stimulation. Naloxone had no effect on the noncholinergic, nonadrenergic stimulation of gastrin levels. These data suggest that endogenous opioids can contribute to vagal gastrin release provided the cholinergic restraint is blocked and adrenergic mechanisms stimulate endogenous opioids. In conclusion a major role of endogenous opioids in the regulation of vagal gastrin release can not be detected.     

Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

Block copolymers with bipyridine containing segments: Synthesis and self-organization by Cu(I) complexation

The synthesis and properties of segmented ABA triblock and (AB)_n multiblock copolymer systems with 6,6′-disubstituted 2,2′-bipyridine (bpy) building blocks B and poly(oxytetramethylene) soft segments A are described. The access to the disubstituted bipyridines in large scale quantities was achieved by modification of conventional synthetic routes. In the presence of copper(I) ions these polymers formed mononuclear [Cu(I)(bpy)₂] complexes in solution through self-assembly. The complexed copolymers were microphase separated systems in bulk with nano to mesoscopic superstructures consisting of copper-bpy complex aggregates in a polyether matrix. The thermal, mechanical and elastomer properties of the block copolymers varied with composition.