Possibility of reducing the luteolytic dose of cloprostenol in cyclic dairy cows

The administration of cloprostenol by intravulvosubmucous (i.v.s.m.) injection at 1 2 and 1 4 of the dose usually given by intramuscular (i.m.) injection, was tested in dairy cows for luteolysis and estrus synchronization. The i.m. injection was used in ten adult cows at the usual dose of 500 mug/animal. Eleven adult cows and 11 heifers were treated i.v.s.m. with a dose equivalent to 250 mug/animal and 125 mug/animal, respectively. Two injections of cloprostenol were administered 11 days apart to the cows not detected in oestrus after a single injection. Forty-three out of the total 46 animals were detected to be in dioestrus at the time of at least one of the injections, as reflected by the plasma progesterone concentrations at the time of treatments. Three out of the 43 animals injected during dioestrus were refractory to the luteolytic effect of cloprostenol; this appeared to be independent of the dosage and the route of administration (refractory cows were: one adult cow treated i.m. and two treated i.v.s.m. with 125 mug of cloprostenol). The mean time interval from injection to the onset of heat was 82.8 hours with a confidence limit for 95% of probability between 67.9 hours and 92.7 hours. The difference between treatments is not significant. The results suggest that in heifers and adult cows cloprostenol can be given i.v.s.m. route at a reduced dose of 1 4 of the usual 500 mug i.m. dosage without affecting the luteolytic effect of the drug or fertility.     

The transsynaptic regulation of the septal-hippocampal cholinergic neurons

There is not yet a complete understanding of the functional interactions among various septal nuclei which regulate hippocampal function. Nevertheless, much has been learned histologically and biochemically about the major connections of the distinct areas of the septal complex and the chemical character of some of these pathways. The cholinergic septal-hippocampal pathway serves as a well defined link between these two important structures of the limbic system. Acetylcholine turnover rates in the hippocampus have been shown to increase or decrease proportionally to the activity of the cholinergic neurons originating in the septum. Moreover, these turnover rates have been shown to be modulated by intraseptal injections of agonists or antagonists of various neurotransmitters or neuromodulators which are stored in various cell groups located in the septum. By coupling this biochemical approach with techniques to study the receptor organization, greater detail concerning the transmitter and cotransmitter interactions among the various neuromodulators can be obtained.     

Characterization and Location of Met5-Enkephalin-Arg6-Phe7 Stored in Various Rat Brain Regions

A specific antiserum against met⁵-enkepha-lin-arg⁶-phe⁷ was raised and used to study the distribution and characterization of met⁵-enkephalin-arg⁶-phe⁷-like immunoreactive material in rat brains by radioimmunoassay and immunohistochemical procedures. The antiserum appears to be directed to the COOH-terminus of the peptide, as it fails to cross-react with met⁵-enkeph-alin, met³-enkephalin-arg⁶, met⁵-enkephalin-arg⁶-arg⁷, met⁶-enkephalin-lys⁶, and leu-enkephalin. However, it cross-reacts with phe-met-arg-phe by about 10% and with phe-met-arg-phe-NH₂ to an insignificant degree. The highest content of met⁵-enkephalin-arg⁶-phe⁷ was found in the striatum, which contains a dense network of immunoreactive varicose fibers and terminals, as well as immunoreac tive cell bodies. The met⁵-enkephalin-arg⁶-phe⁷ in striatum can be released in a Ca²⁺-dependent manner by a depolarizing concentration of KC1, raising the possibility of a neu-roregulatory role for met⁵-enkephalin-arg⁶-phe⁷. Characterization of the immunoreactive material by gel filtration and high pressure liquid chromatography revealed the presence of multiple forms of immunoreactive material in some brain regions.     

Opioid antinociception and positive reinforcement are mediated by different types of opioid receptors

Fentanyl (FEN) and diprenorphine's (DIPR) potentials for analgesia and reinforcement were assayed using rats. Analgesia was measured by the classic tail-flick test. The test germane to opioid reinforcement involved measuring pressing rates for direct electrical stimulation of the lateral hypothalamus and ventral tegmental area. FEN, as does morphine and heroin, produced strong analgesia and enhanced pressing rates for brain stimulation. DIPR produced no analgesia and antagonized FEN's analgesia. DIPR, at doses antagonizing FEN's analgesia, enhanced pressing for brain stimulation. DIPR's enhancement of pressing was antagonized by naloxone (100 micrograms/kg). When FEN and DIPR were given concurrently, pressing for brain stimulation was not reduced and was greater than after FEN alone was given. These data support a conclusion that different types of receptors are associated with opioid analgesia and reinforcement.     

Muscarinic Receptors Modulate Dopamine-Activated Adenylate Cyclase of Rat Striatum

We investigated the effect of acetylcholine (ACh) on the activation of adenylate cyclase by dopamine (DA) in a lysed synaptosomal preparation from rat striatum. ACh reduced both basal and the DA-activated adenylate cyclase with an apparent IC50 of approximately 1 microM. From a kinetic analysis it appeared that ACh reduced the Vmax for activation by DA but not the activation constant for DA. For most preparations the Vmax was reduced by 30-40%. The presence of atropine did not affect the activation of the enzyme by DA but it blocked the inhibition by ACh. Following 6-hydroxydopamine lesion of the nigrostriatal pathway, the enzyme became supersensitive to activation by DA and also more sensitive to inhibition by ACh. Inhibition of adenylate cyclase by ACh appeared to be rather specific for activation by DA, as ACh had no effect on activation of adenylate cyclase by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. These results indicate that some striatal muscarinic and dopaminergic receptors are probably coupled to the same adenylate cyclase domain. Moreover, they suggest a biochemical model for the dynamic balance of cholinergic and dopaminergic neurons that innervate the striatum.     

In vitro assessment of the toxicity of metal compounds

A review has been compiled illustrating the directions taken in examining the genotoxic effects of metals and their compounds centering only on those studies pertaining to effects of metals and their compounds on DNA structure and function, such as the induction of DNA strand breaks, production of DNA-protein crosslinks, induction of chromosomal aberrations, and sister chromatid exchanges. Although it is premature to declare a cause and effect relationship between the carcinogenic activity of metals and their ability to induce one or more lesions in DNA, strong evidence is emerging to suggest such a relationship. Low concentrations of metals induce the appearance of DNA lesions, such as strand breaks and crosslinks, or induce sister chromatid exchanges or DNA repair synthesis. Assays based upon these events constitute extremely sensitive probes for genotoxic effects of metals and their compounds. These effects of metals on DNA are consistent with the currently accepted mechanism of chemical carcinogenesis, allowing the acquisition and propagation of altered DNA function. The lack of complete information on the activity of metals in producing DNA lesions allow only preliminary conclusions to be drawn. Certain compounds containing potentially or actually carcinogenic elements, such as Ni, Be, As, Cr, Cd, and to a minor extent Pb, have yielded positive responses in one or more DNA lesion assays. At relatively nontoxic levels of Ni and Cr, considerable evidence suggests that multiple types of DNA lesions are induced.     

PROTEIN METABOLISM AND AMINO ACID ACCUMULATION IN THE RAT SUBMAXILLARY GLAND DURING REDUCED SYMPATHETIC ACTIVITY

Abstract— Unilateral sympathetic decentralization of the superior cervical ganglion of rats was performed 3 days prior to the experiments. A two-compartment kinetic model was proposed to describe the effect of decentralization on (1) the uptake of a nonphysiological amino acid from plasma to the submaxillary gland and (2) the incorporation of a physiological amino acid from precursor pool into protein. The calculations based on the model showed that the fractional rate constant for efflux of the nonphysiological amino acid, α-[3-¹⁴C] aminoisobutyric acid, was greater in the decentralized than in the normal gland. However, efflux rate was equal in the two glands because the extrapolated zero time value of the initial concentration was greater in the normal gland.
The labelled physiological amino acid, [¹⁴C]leucine, was used in initial experiments to assess turnover rate of the gland proteins but it was rapidly metabolized to many other radioactive compounds. Therefore, arginine[¹⁴C]guanido was employed-arginine being the only labelled amino acid found after injection. Since the steady state content of submaxillary gland proteins was not changed but the fractional rate constant of conversion of free arginine into protein (k_p) was greater in the decentralized gland (k_p= 0-40 h^_l) than in the normal (k_p= 0-27 h⁻¹), we can conclude that decentralization increases protein turnover rate; thus, assuming that arginine[¹⁴C]guanido is homogeneously distributed in the tissue pools of free arginine, the rate of protein turnover is greater in the sympathetically decentralized gland than in the normal.     

The action of α-amanitin in vivo on the synthesis and maturation of mouse liver ribonucleic acids

α-Amanitin acts in vitro and in vivo as a selective inhibitor of nucleoplasmic RNA polymerases. Treatment of mice with low doses of α-amanitin causes the following changes in the synthesis, maturation and nucleocytoplasmic transfer of liver RNA species. 1. The synthesis of the nuclear precursor of mRNA is strongly inhibited and all electrophoretic components are randomly affected. The labelling of cytoplasmic mRNA is blocked. These effects may be correlated with the rapid and lasting inhibition of nucleoplasmic RNA polymerase. 2. The synthesis and maturation of the nuclear precursor of rRNA is inhibited within 30min. (a) The initial effect is a strong (about 80%) inhibition of the early steps of 45S precursor rRNA maturation. (b) The synthesis of 45S precursor rRNA is also inhibited and the effect increases from about 30% at 30min to more than 70% at 150min. (c) The labelling of nuclear and cytoplasmic 28S and 18S rRNA is almost completely blocked. The labelling of nuclear 5S rRNA is inhibited by about 50%, but that of cytoplasmic 5S rRNA is blocked. (d) The action of α-amanitin on the synthesis of precursor rRNA cannot be correlated with the slight gradual decrease of nucleolar RNA polymerase activity (only 10–20% inhibition at 150min). (e) The inhibition of precursor rRNA maturation and synthesis precedes the ultrastructural lesions of the nucleolus detected by standard electron microscopy. 3. The synthesis of nuclear 4.6S precursor of tRNA is not affected by α-amanitin. However, the labelling of nuclear and cytoplasmic tRNA is decreased by about 50%, which indicates an inhibition of precursor tRNA maturation. The results of this study suggest that the synthesis and maturation of the precursor of rRNA and the maturation of the precursor of tRNA are under the control of nucleoplasmic gene products. The regulator molecules may be either RNA or proteins with exceedingly fast turnover.