Dopamine receptors,controlling dopamine levels in rat adrenal glands — comparison with central dopaminergic autoreceptors

Summary Previous work in this laboratory, as well as observations reported in the literature, indicate that the adrenal medulla contains dopamine (DA) receptors of the D-2 subtype, which among other things are capable of controlling the DA level in rat adrenal glands. To further characterize the DA receptors involved in the control of the adrenal DA level, the effects of 9 DA receptor agonists with various intrinsic activities were compared. After various periods of drug administration the rats were killed by decapitation and the DA content of the adrenal glands and the DOPAC content of the forebrain were measured by high-performance liquid chromatography with electrochemical detection. All the investigated DA receptors agonists caused an increase in adrenal DA level, although statistical significance was not reached in one case /(–)-HW165/. Domperidone, a DA D-2 receptor antagonist which does not readily cross the blood brain barrier, blocked the DA-elevating effects of apomorphine, quinpirole, B-HT 920 and both enantiomers of 3-PPP. For the two ergolines terguride and SDZ 208-920 the blockade by domperidone was not complete, suggesting that their effects are mediated not only through DA, but also through other receptor systems. The dose of domperidone used (3 mg/kg) had but a marginal influence on brain DOPAC levels, supporting the almost exclusively peripheral effect of this agent. Our data indicate that the DA D-2 receptors which control the DA level in the adrenal medulla in rats, have characteristics similar to, though not identical with the autoreceptors in the forebrain.     

The intrinsic activities of the partial dopamine receptor agonists (-)-3-PPP and TDHL on pituitary dopamine receptors are lower in female than in male rats

The abilities of the mixed agonists/antagonists on dopamine (DA) receptors, (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [-)-3-PPP) and transdihydrolisuride (TDHL), to suppress serum prolactin levels in acutely hyperprolactinemic male and female rats were investigated. gamma-Butyrolactone was used to deplete endogenous DA and raise serum prolactin concentrations. Both (-)-3-PPP and TDHL were found to cause sexually differentiated responses: (-)-3-PPP reduced serum prolactin levels dose dependently and effectively in males but caused only a modest decrease of prolactin release in females. Moreover, (-)-3-PPP antagonized the prolactin-suppressing effects induced by the DA receptor agonist (+)-3-PPP in females. Likewise TDHL decreased prolactin secretion markedly in males while it had only slight effects in females. It can be concluded from these results that the intrinsic activities of the partial DA agonists (-)-3-PPP and TDHL are lower in female than in male rats, suggesting a reduced responsiveness of hypophyseal DA receptors in females. Since DA levels in the pituitary portal circulation are higher in female than in male rats, this study gives further support to the hypothesis claiming an inverse relationship between the intrinsic activity of a mixed agonist/antagonist and the degree of previous stimulation of its receptor.     

Marked locomotor stimulation in monoamine-depleted mice following treatment with atropine in combination with clonidine

Summary The present study demonstrates that the muscarinic antagonist atropine and the -adrenergic agonist clonidine, though ineffective when administered separately, produced a pronounced locomotor stimulation in monoamine-depleted mice when combined. The atropine + clonidine-induced locomotor stimulation was counteracted by both the ₂-adrenoceptor antagonist idazoxan and the acetylcholinesterase inhibitor physostigmine. Thus, it is clear that simultaneous manipulations with cholinergic and adrenergic systems are as effective in restoring locomotion in monoamine-depleted mice as increasing central dopaminergic tone. This finding may have implications for the treatment of a movement disorder like Parkinson's disease.     

Differential responses in post- and pre-ganglionic adrenal sympathetic nerve activity and renal sympathetic nerve activity after injection of 2-deoxy-D-glucose and insulin in rats.

The aim of the study was to compare pre-ganglionic adrenal nerve activity (pre-aSNA) to post-ganglionic adrenal nerve activity (post-aSNA) in rats after administration of 2-deoxy-D-glucose (2-DG, 500 mg kg-1, i.v.), which mimicks a central hypoglycaemia or to the response in pre-aSNA and post-aSNA to hypoglycaemia after injection of insulin (5U). Renal postganglionic sympathetic nerve recordings (rSNA) in a separate group was used as a reference. Adrenal or renal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar-rats. Trimethaphan, a short-lasting ganglionic blocker, was administered i.v. (10 mg kg-1) in order to test for pre- or post-aSNA in the adrenal nerves. The adrenal nerves was considered to contain predominantly post or preganglionic fibres, respectively if the nerve activity in the adrenal nerve decreased (post-aSNA) or increased (pre-aSNA). In contrast, all renal nerves showed almost a pure postganglionic activity. Post-aSNA responded with a tendency to increase after the 2-DG injection. The highest value (percentage change from control) 5 min after injection was 12 +/- 9%. The pre-aSNA increased with values of 99 +/- 52% at 3 min and 86 +/- 31% at 5 min (percentage change from control). The activity in the rSNA was only slightly decreased after the injection of 2-DG when compared to pre-drug control activity. There was a significant difference between the pre-aSNA vs. post-aSNA at 1 min (P less than 0.05), 3 min (P less than 0.01) and 5 min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-actin specificity of human smooth muscle antibodies in chronic active hepatitis.

Thirty sera reacting by IFL technique in titres greater than or equal to 100 with smooth muscle fibres of rat stomach, rat renal glomeruli, and with the membrane region of thyroid cells were randomly chosen among sera sent in for routine testing of tissue antibodies. All sera but one were found to be derived from patients with chronic active hepatitis. The smooth muscle and other relevant cell staining were abolished after absorption of sera with actin, prepared from rabbit skeletal muscle and found to be homogeneous by SDS gel-electrophoresis and by electron microscopy. The actin anti-bodies were purified by precipitation of sera with F-actin and elution of the precipitates at acid pH. The purified antibodies stained all tissues in the same way as the original sera. In double immunodiffusion tests all thirty sera gave precipitation with actin. Thus, it was concluded that these broad-reacting SMA are directed against actin. The finding of high-titred SMA is of diagnostic value and supports the clinical diagnosis of active chronic hepatitis. In addition, anti-actin antibodies eluted from human sera are a suitable tool for studying actin-containing cellular structures.     

Potentiation by sulfide of hydrogen peroxide-induced killing of Escherichia coli.

L-Cysteine potentiates 100-fold the hydrogen peroxide-induced killing of a growing culture of Escherichia coli K-12 (Berglin et al., J. Bacteriol. 152:81-88). In the present study it is shown that hydrogen sulfide is formed from L-cysteine and that sodium sulfide could substitute for L-cysteine in the potentiation of hydrogen peroxide-induced killing of E. coli K-12. Addition of an amino acid, L-leucine, L-valine, or L-alanine, to an L-cysteine-containing medium with a growing culture of E. coli K-12 inhibited hydrogen sulfide formation and the potentiation of hydrogen peroxide-induced killing. These amino acids did not inhibit hydrogen sulfide formation from L-cysteine by a cell extract, and they did not inhibit the potentiation by sulfide of hydrogen peroxide-induced killing. This indicated that the amino acids protected the culture from L-cysteine-potentiated, hydrogen peroxide-induced killing by inhibiting the transport of L-cysteine into the cell. The potentiation by sodium sulfide of hydrogen peroxide-induced killing was abolished by the metal ion chelator 2,2'-bipyridyl. This indicated that metal ions, in addition to sulfide, were involved in the killing. Toxic effects of hydrogen peroxide are often presumed to be mediated by hydroxyl radicals formed in iron-catalyzed reactions. It was demonstrated that iron sulfide was more efficient than ferrous iron in catalyzing the formation of hydroxyl radicals from hydrogen peroxide. It was suggested that hydrogen sulfide formed in polymicrobial infections may play an important role in the host defense by potentiating the antimicrobial effect of hydrogen peroxide produced by phagocytic cells.     

Secretory IgA and IgM antibodies to E. coli O and poliovirus type I antigens occur in amniotic fluid,meconium and saliva from newborns. A neonatal immune response without antigenic exposure: a result of anti-idiotypic induction?

Antibodies to E. coli O-antigens and poliovirus type I antigen as well as total SIgA were analysed using enzyme-linked immunosorbent assay (ELISA), in amniotic fluid and in meconium, urine and saliva from neonates. Secretory IgA and IgM antibodies to E. coli and poliovirus antigens were found in saliva as well as in most meconium samples taken during the first day of life. SIgA could be quantified in all types of samples including amniotic fluid. The finding of secretory IgA and IgM antibodies to E. coli and poliovirus type I antigens in early samples from an infant of a hypogammaglobulinaemic mother, given regular intravenous (i.v.) immunoglobulin prophylaxis, but still lacking IgA and IgM antibodies, supports a fetal origin for at least part of the secretory antibodies detected in the different samples. Since it is unlikely that the fetus has been exposed to poliovirus, which is rare in Sweden, it is hypothesized that the stimulus inducing the SIgA and IgM antibodies found in the neonate could be anti-idiotypic antibodies from the mother.     

Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol

Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B₁, B₆, B₁₂ (Neurobion^®) as well as of vitamin B₆ administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED₅₀ of Neurobion^® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B₆ is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion^® and vitamin B₆ are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion^® or vitamin B₆ were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion^® or vitamin B₆was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion^® is largely due to vitamin B₆. Vitamin B₁₂ may contribute to this effect, whereas vitamin B₁ alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion^® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion^® but may be enhanced after repeated administration of the compound.     

Radiation dose measurements with alanine/agarose gel and thin alanine films around a 192Ir brachytherapy source,using ESR spectroscopy

Alanine/agarose gel and alanine films in stacks have been used for measurements of absorbed dose around an HDR 192Ir source in a vaginal cylinder-applicator, with and without a 180 degrees tungsten shield. The gel and the films were analysed by means of ESR spectroscopy and calibrated against an ion chamber in a 4 MV photon beam to obtain absolute dose values. The gel serves as both dosimeter and phantom material, and the thin (130 microm) films are used to achieve an improved spatial resolution in the dose estimations. Experimental values were compared with Monte Carlo simulations using two different codes. Results from the measurements generally agree with the simulations to within 5%, for both the alanine/agarose gel and the alanine films.