Ca2+ channel antagonist actions in bladder smooth muscle: comparative pharmacologic and [3H]nitrendipine binding studies

The actions of a series of 15 Ca2+ channel antagonists including D-600, nifedipine, and diltiazem were examined against K+ depolarization and muscarinic receptor induced responses in guinea pig bladder smooth muscle. Responses of bladder are very dependent upon extracellular Ca2+ and sensitive to the Ca2+ channel antagonists, the tonic component more than the phasic component of response. Regardless of stimulant, K+ or methylfurmethide (MF), or component of response, the same rank order of antagonist activities is expressed, suggestive of a single structure-activity relationship and the existence of a single category of binding site which may, however, exist in several affinity states. High affinity binding of [3H]nitrendipine (KD = 1.1 X 10(-10) M) occurs in bladder membranes, and similar high affinity binding was found in microsomal preparations from other smooth muscles including guinea pig and rat lung, rat vas deferens, uterus, and stomach. [3H]nitrendipine binding in the bladder was sensitive to displacement by other 1,4-dihydropyridines, paralleling their pharmacologic activities and showing excellent agreement with binding data previously obtained for guinea pig ileal smooth muscle. Comparison of pharmacologic data for inhibition of K+- and MF-induced responses by a common series of Ca2+ channel antagonists in bladder and ileum revealed excellent correlations. Neither pharmacologic nor binding studies suggest significant differences in Ca2+ channel antagonist properties in smooth muscle from bladder and intestine.     

Nonintegrative transformation in the filamentous fungus Podospora anserina: stabilization of a linear vector by the chromosomal ends of Tetrahymena thermophila.

The effect of the chromosomal ends of Tetrahymena thermophila on the stability of linear transforming molecules in the filamentous fungus Podospora anserina was tested. A derivative of an integrative vector for this fungus has been constructed, so that after linearization, the ends of the plasmid are the telomeric sequences of T. thermophila. After transformation, this linear molecule was maintained as an extrachromosomal plasmid with no integrated copies in about 50% of the transformants. Under selective conditions, there was approximately one linear molecule per 5 to 10 nuclei, and these extrachromosomal molecules were rapidly lost under nonselective conditions. The circular plasmid carrying an inverted repeat of T. thermophila telomeres could be linearized and processed in vivo.     

Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages

Maleylated bovine serum albumin (maleyl-BSA) and other polyanionic polymers that are recognized by cell surface receptors on macrophages have been shown to induce chemotaxis, protease secretion, and tumoricidal function in this cell type. In this paper the effect of maleyl-BSA on Ia antigen expression has been evaluated. In a fashion similar to LPS, maleyl-BSA suppressed IFN-gamma-induced expression of Ia in a time- and dose-dependent manner. Also like LPS, maleyl-BSA stimulated the production and secretion of substantial amounts of PGE2 over a 24-hr period. This did not, however, appear to be the primary mechanism by which expression of Ia was suppressed, because co-treatment of the cells with indomethacin, which totally inhibited the production of PGE2, only minimally affected the suppressive activity. Surprisingly, the suppressive activity of both maleyl-BSA and LPS could be largely abrogated by co-treatment of the cells with cyclohexamide during the time period when Ia expression was sensitive to suppression. This effect was selective in that PGE2- or dibutyryl cyclic AMP-induced suppression of Ia expression was not affected by cyclohexamide treatment. The data support the concept that there are multiple molecular mechanisms involved in the negative regulation of IFN-gamma-induced Ia expression in macrophages. Such mechanisms may include, in addition to the synthesis of PGE2 and consequent elevation in intracellular levels of cyclic AMP, one or more proteins made early after treatment with either maleyl-BSA or LPS. Thus the function of some of these early gene products may be to regulate expression of functional genes such as that encoding Ia antigen.     

Influence of oxytocin on human memory processes: Validation by a control study

An earlier report (1) of an adverse effect of high doses of oxytocin on human memory included results of studies on women receiving oxytocin as part of the treatment to induce 2nd trimester therapeutic abortion. These women served as their own controls. We have now been able to study a group of women who have been treated in all ways like the original group, with the exception that they did not receive oxytocin. The results from this external control corroborate the finding that oxytocin affected memory.     

Conus-like structure in the eye of the deep-sea teleost Radiicephalus elongatus (Pisces,Teleostei)

Summary A conus-like structure, the hyaloid conus, located on the optic nerve head of the mesopelagic deep-sea teleost Radiicephalus elongatus is described. The hyaloid conus consists of a tapering sheath of unpigmented, vascularized connective tissue enveloping the proximal part of the hyaloid artery which proceeds from the optic nerve head through the vitreous body to the ventrally located falciform process and lens muscles. The hyaloid artery passes through the hyaloid conus without giving off any branches. The conus vessels encircling the hyaloid artery receive arterial blood from the choroid via small arteries and are drained to the choroid by a single vein. The hyaloid conus is compared with the lacertilian conus papillaris. The function of the hyaloid conus is unknown. Because of its small dimensions relative to those of the eyeball and its few capillaries, it is unlikely that the hyaloid conus is a supplemental nutritive device for the retina.     

Hepatic reactions in erythropoietic protoporphyria (author's transl)

The main hepatic change in erythropoietic protoporphyria is the deposition of protoporphyrin. Brown deposits of this pigment occur in bile canaliculi and ductules, discretely in hepatocytes, and secondarily in macrophages and Kupffer cells. The pigment is deposited in a crystalline form. Under the fluorescence microscope with a mercury maximum pressure burner (HO 50) at a wave length of 380--500 nm, it shows a typical red fluorescence even after paraffin embedding. Its crystalline structure results in a characteristic double refraction under the polarising microscope. Light-microscopically, hepatocellular reactions are characterised mainly by discrete alterations in the ergastoplasm. However, cell damage is indicated by diffusely distributed, hyaline single cell necrosis and by cytolytic piecemeal necrosis at the peripheries of hepatic lobules. Numerous, often disturbed mitoses produce binuclear and multinuclear hepatocytes. The obligatory secretion of protoporphyrin into the bile ducts leads to an alteration in the canalicular and ductular excretion apparatus which involves distinct ductular proliferation and accompanying fibrosis. Piecemeal necrosis is a further consequence of this process. The resulting histological picture is similar to sclerosing cholangitis with which it also has in common the slowly progressive development of hepatic cirrhosis.     

Mechanism of action of ryanodine on cardiac sarcoplasmic reticulum

Ryanodine was found to initially inhibit calcium uptake by cardiac sarcoplasmic reticulum. This initial depression was followed by a later marked stimulation of calcium uptake. These effects were noted when calcium uptake was measured in the presence or absence of oxalate. The requirement for preincubation with ryanodine was highly dependent on ryanodine concentration and temperature. The mechanism of action of ryanodine clearly was not an effect on oxalate entry or calcium oxalate precipitation because the effects were also observed in the absence of oxalate. Ryanodine also had no effect on passive calcium efflux from actively loaded vesicles. Because ryanodine had no effect on Ca2+-ATPase activity under defined conditions of an ATP-regenerating system and no calcium gradient, we suggest ryanodine does not change the stoichiometry of the pump. Our results are consistent with the hypothesis that ryanodine closes a calcium channel in a subpopulation of the vesicles.