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L Löfberg

Publications and source records attributed to L Löfberg.

12 recordsLinked to original sources

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

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 [(-)-HW 165]. 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.

3,4-Dihydroxyphenylacetic Acid

The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat.

The effects of dopamine-depleting 6-OHDA infusions in the ventral or dorsal striatum on maternal and sexual behaviors were examined in female rats. Like sham-operated controls, lactating rats receiving 6-OHDA in the ventral striatum built good nests, nursed the infants and showed maternal aggression toward strange intruders. By contrast, the lesioned females performed poorly in tests for pup retrieval, as reflected in greatly protracted retrieval latencies. There was no effect of ventral striatal DA depletions on proceptive and receptive elements of female sexual behavior, which was studied after lactation following ovariectomy and exogenous administration of ovarian hormones, but these animals did show an attenuated hyperactivity response to a low dose of amphetamine. Females with dopamine lesions in the dorsal striatum did not differ from controls with respect to maternal and sexual behavior, but they did show an enhanced hyperactivity response to amphetamine treatment.

Amphetamine

Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness.

The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions.

Animals

Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent.

The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.

3,4-Dihydroxyphenylacetic Acid

Acute changes in dopamine levels in rat adrenal glands after administration of dopamine receptor agonists and antagonists.

The study was aimed at in vivo pharmacological identification of the possible dopamine (DA) receptor(s) involved in changes of the DA level in rat adrenal glands. Previous work in this laboratory has shown that the DA level is largely controlled by the rate of catecholamine synthesis. The rats were killed by decapitation after various periods of drug administration and the catecholamine content of adrenal glands and forebrain was measured by high-performance liquid chromatography with electrochemical detection. Administration of the DA D-1 + D-2 receptor agonist, apomorphine, induced a statistically significant increase in DA levels in the adrenal glands. The same effect was noted after administration of the DA D-2 receptor agonist, quinpirole. The DA D-2 receptor antagonist, raclopride, blocked the apomorphine-induced increase in adrenal DA levels but had no effect per se on these levels. The DA D-1 receptor agonist, SKF 38393, and the DA D-1 receptor antagonist, SCH 23390, did not have any effect on apomorphine-induced changes in DA content in the adrenals. The DA elevating effect of the DA D-2 receptor agonist, quinpirole, in the adrenals was completely blocked by the DA D-2 receptor antagonist, domperidone. This compound does not cross the blood-brain barrier readily and is thus supposed to act mainly on peripheral tissues. In support of this, the dose of domperidone used did not affect brain DOPAC levels. Our data, together with observations reported in the literature, indicate that the adrenal medulla contains DA receptors of the D-2 subtype, which are capable of controlling the DA level in rat adrenal glands.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Direct-vision sampling of chorionic villi during extra-amniotic instillation of physiologic saline solution: effect on intrauterine pressure and fetal heart activity.

After 150 ml of physiologic saline solution had been infused into the extra-amniotic space before first-trimester vacuum aspiration abortion, intrauterine pressure ranged between 16 and 23 mm Hg, thus not more than during Braxton Hicks contractions. At chorionic villi sampling during continuous saline solution infusion, fetal heart activity (beats per 15 seconds) decreased temporarily from about 36 to about 33.

Amnion

In vivo displacement by 3-PPP enantiomers of N,N-dipropyl-5,6-ADTN from dopamine receptor-binding sites in rat striatum.

The enantiomers of 3-PPP or haloperidol were injected in various doses to rats 1 hour after the established dopamine receptor ligand N,N-dipropyl-5,6-ADTN. After another 40 minutes the binding of the ligand to the striatum was measured by high performance liquid chromatography, using the level in the cerebellum as "blank". (-)-3-PPP was found to cause a maximum 71% displacement of the ligand from the striatal binding sites. Haloperidol proved to be more potent but not significantly more efficacious in displacing the ligand. However, the combined treatment with (-)-3-PPP and haloperidol caused a stronger displacement of the ligand than (-)-3-PPP alone, suggesting that the binding-site populations available for the two agents are not fully identical. (+)-3-PPP also caused displacement of the ligand but was considerably less potent than its enantiomeric twin. The results are discussed against the background of the different pharmacological profiles of the 3-PPP enantiomers and haloperidol. It is suggested that an inverse relationship may exist between receptor affinity and intrinsic activity and that such a relationship may be inherent in the mechanism underlying receptor stimulation.

Animals

First-trimester diagnosis on chorionic villi obtained by direct vision technique.

An improved technique for direct vision chorionic biopsy that gives a clear view of the amniotic sac was developed. With this technique, used in 48 women prior to vacuum aspiration and in six cases for diagnosis (karyotyping or enzyme analysis), it was possible to obtain chorionic villi free from contamination by maternal tissue. It was also possible to pick out villi (rich in blood vessels and with abundant buds on their surface) found to be most capable of growing in vitro. In the diagnostic cases, the pregnancies have continued uneventfully since the sampling; one pregnancy is now in the 32nd week.

Adult

"Blind" versus direct vision technique for fetal skin sampling in cases for prenatal diagnosis.

Seven fetuses at risk of developing a serious inherited skin disorder (epidermolysis bullosa atrophicans generalisata gravis in 4, bullous ichthyosiform erythroderma in 2, and non-bullous ichthyosiform erythroderma in 1) were subjected to prenatal diagnosis by fetal skin sampling. The conventional "blind" biopsy procedure was used in the first 3 cases; a two-cannula technique (one cannula for the optic instrument and the other for the biopsy forceps) that permits biopsy of the skin under direct vision, was employed in the remaining 4 cases. With the "blind" technique, 8 to 10 biopsy specimens had to be taken to ensure that enough skin material would be available for the microscopic examination; only one specimen out of every two was found to consist of skin; the remainder comprised fetal membranes, myometrium, or trophoblast. In one case where the "blind" procedure has been used, leakage of amniotic fluid occurred and labor started in the 33rd week. With the two-cannula technique, the number of biopsy samples could be confined to two or three, and all proved to be of skin.

Biopsy

Prenatal exclusion of Herlitz syndrome by electron microscopy of fetal skin biopsies obtained at fetoscopy.

Two women had each borne a child who had died of Herlitz syndrome, i.e., epidermolysis bullosa atrophicans generalisata gravis. In subsequent pregnancies, the women requested prenatal diagnosis. Samples of skin from the two fetuses were obtained at fetoscopy in the 19th week of gestation. In both cases the disorder could be ruled out prenatally on the basis of ultrastructural demonstration of the regular presence of normal hemidesmosomes with well-developed sub-basal dense plates at the dermo-epidermal junction. The infants were subsequently born and had normal skin, the sites of fetal skin biopsies showing no scarring.

Epidermolysis Bullosa

Fetoscopy.

A brief report is given on fetal blood sampling by fetoscopy in three fetuses at risk for severe congenital bleeding disorder; hemophilia A in two cases, von Willebrand's disease in one. Published reports on complications of fetoscopy are reviewed. Out of all together about one hundred pregnancies that have been allowed to continue after fetoscopy, five ended in miscarriage. No other serious complication has been reported.

Abortion, Spontaneous