Leena Tuomisto

Histamine and histamine-N-methyltransferase in the CSF of patients with multiple sclerosis

The CSF of twenty-six patients with multiple sclerosis (MS) and of twelve control persons was analysed for histamine and histamine-N-methyltransferase (HMT) activity. Both in patients with remitting and progressive type of disease the histamine level was about 60% higher than in the controls. On the other hand in both groups of patients the HMT activity was significantly lower (32% and 40% respectively) than that of controls. These results suggest an altered histamine metabolism in MS. This might be associated with the immune reaction in MS brain.

Vasopressin release by histamine in the conscious goat

The vasopressin releasing activity of histamine was studied in conscious goats. Histamine was infused into the brain ventricles or intravenously and serial blood samples were taken from the jugular vein. Plasma vasopressin was assayed by a radioimmunoassay for arginine vasopressin (AVP). After i.v. infusions of 300 micrograms and 1 mg of histamine, a pronounced increase in plasma AVP up to greater than 100 pg/ml occurred. This was considered secondary to hypotension, since it only occurred with doses that markedly decreased arterial blood pressure. When given i.c.v. even smaller doses of histamine increased plasma AVP without any concomitant decrease in blood pressure. There was a simultaneous decrease in renal free water clearance in hydrated animals. Up to the dose of 300 microgramshistamine, the increase in AVP was modest. Histamine 1 mg i.c.v., given to either hydrated or non-hydrated animals, increased plasma AVP about tenfold, up to 38.3 +/- 23.3 pg/ml and 56.7 +/- 19.0 pg/ml, respectively. In individual experiments the correlation between the AVP level and the degree of antidiuresis was less apparent, since the kidney seemed to be very sensitive even to small changes in plasma AVP. It is concluded that histamine releases vasopressin through a central mechanism and it is reasonable to suppose that histamine may act as a neurotransmitter in the vasopressin releasing system.

Inhibition of monoamine uptake in synaptosomes by tetrahydroharmane and tetrahydroisoquinoline compounds

SummaryThe effect of some tetrahydroharmane derivatives on the synaptosomal uptake of monoamines was studied. 1,2,3,4-Tetrahydroharmane (TH), which can be viewed as an analog of tryptamine, inhibited 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) uptake, but TH was about 10 times less potent than tryptamine. 6-Hydroxy-1,2,3,4-tetrahydroharmane (6-HTH), a 5-HT analog, was slightly more potent an inhibitor of 5-HT uptake than TH, but as catecholamine uptake inhibitors these compounds were equipotent. Harmane-1,2,3,4-tetrahydro-3-carboxylic acid had no effect. Salsolinol and salsolidine, tetrahydroisoquinoline derivatives, were less potent than the harmane derivatives. It is to be concluded that also tetrahydroharmane derivatives have an affinity to the amine “pump” similarly to that of the tetrahydroisoquinolines, which are the corresponding analogs of catecholamines. These kinds of compounds are important because of the possibility that they may be formed in physiological conditions as condensation products of biogenic amines and aldehydes, e.g. acetaldehyde, which is an intermediate of ethanol metabolism.

Antidiuresis induced by infusions of histamine into the brain ventricles of conscious hydrated goats.

Histamine was infused into the third or lateral ventricle of conscious hydrated goats, and urine samples were analyzed for volume, osmolality and electrolytes. Doses of 10--1000 microgram of histamine induced dose-dependent antidiuretic responses both as to the maximum osmolality and the duration of the osmolality increase. Urine osmolality began to rise within a few minutes, reached its maximum within 0.5--2 h and was elevated for 1.5--4 h, depending on the dose. Thereafter a second increase in osmolality often occurred, which lengthened the effect of histamine dose-dependently up to about 10 h with the largest dose of histamine. Histamine (50--300 microgram) and the control solution given into the lateral ventricle increased the excretion of Na+ into the urine. After the largest dose of histamine (1000 microgram), however, the excretion of Na+ was significantly lower than in the control experiments. After the larger doses of histamine, effects on motor or autonomic functions were seen. These included decreased spontaneous motor activity, increased respiratory rate, defecation and miosis. It is suggested that the site of action of histamine is central, and that the release of vasopressin through the activation of the neurosecretory system is probably involved. In addition the changes in electrolytes may suggest an involvement of the release of other factors such as prolactin.

In vivo release of endogenous catecholamines, histamine and GABA in the hypothalamus of Wistar Kyoto and spontaneously hypertensive rats

SummaryThe release of dopamine, noradrenaline, adrenaline, histamine and GABA was studied in the posterior hypothalamus of conscious, freely moving Wistar Kyoto (WKy) rats and spontaneously hypertensive (SH) rats (Okamoto strain). A guide cannula was stereotaxically inserted under anaesthesia. Some days later a push-pull cannula was inserted into the guide cannula so that the tip of the push-pull cannula reached the posterior hypothalamic nucleus. The posterior hypothalamic nucleus of the freely moving animal was superfused with artificial CSF. The rates of release of the neurotransmitters were determined in the superfusate which was continuously collected in 10 min periods.In SH rats, the rates of resting release of dopamine and histamine were higher than in WKy rats, while the rates of release of noradrenaline and adrenaline in SH rats were lower than those in WKy rats. No significant differences were found in the rates of resting release of GABA between SH and WKy rats. Superfusion of the posterior hypothalamic nucleus of WKy rats with KCl-rich CSF (60 mmol/1 KCl) significantly increased the rates of release of noradrenaline and adrenaline, while those of dopamine and GABA tended to be enhanced. In SH rats, hypothalamic superfusion with KCl-rich CSF increased the rates of release of dopamine, noradrenaline, adrenaline and GABA. The KCl-induced release of neurotransmitters did not differ between SH and WKy rats. Superfusion with KCl-rich CSF did not influence the rates of release of histamine either in SH or in WKy rats.The findings indicate that differences exist in the resting release of dopamine, noradrenaline, adrenaline and histamine between SH and WKy rats. Our experimental set-up seems to be useful in investigating neurochemical changes in distinct brain areas of animals at different physiopathologic stages under in vivo conditions.

Ontogenesis and regional distribution of histamine and histamine-N-methyltransferase in the guinea pig brain.

The ontogenetic development and the regional distribution of histamine (HA) and histamine‐N‐methyltransferase (HMT, EC 2.1.1.8) in guinea pig brain and pituitary gland were studied. The samples were taken every fourth day beginning on the 28th foetal day. The HA concentration in the brains of the youngest foetuses was almost undetectable. A significant increase in HA concentrations occurred between days 40 and 44, which coincides with the period of rapid growth of nerve cell processes in this species. After this, a steep increase continued to the end of gestation in the hypothalamus, and to a lesser degree in the medulla‐midbrain and in the forebrain. In all parts of the brain the adult HA levels were reached by the time of birth. The HMT activity increased 15‐fold from the 28th foetal day to the adult and reached ca. 80% of the adult activity by the time of birth. The HMT activity developed earlier in the midbrain than in the forebrain or in the cerebellum, but after the birth the regional distribution of HMT was fairly even. In the pituitary gland the HA concentration and HMT activity increased hundredfold and tenfold, respectively.

Vasopressin Levels in the Cerebrospinal Fluid in Rats of Different Age and Sex

In male and female rats of two different age groups, we measured the arginine-vasopressin (AVP) levels in cerebrospinal fluid (CSF) collected at different times of the day. Mean values of AVP in cisternal CSF averaged across the different times of the day were higher in males than in females (p = 0.02), and in young (2 months) than in aged (12 months) rats (p = 0.03) of both sexes. The AVP levels in CSF showed a clear circadian rhythm in both young and aged male rats; the values at 07.00 h and 13.00 h were higher than those at 01.00 h and 19.00 h. The amplitude of the rhythm was smaller in females than in males. In addition, the rhythm was more pronounced in young than in aged rats of both sexes. These data suggest that both age and sex affect levels of vasopressin in CSF.

Taurine in the osmoregulation of the Brattleboro rat

The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and 3H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

Cardiovascular and behavioural changes after i.c.v. infusions of histamine and agonists in conscious goat

Histamine (3 and 10 μmoles) raised the blood pressure in the conscious goat when given i.c.v. but lowered it when given intravenously. The results with 2-PEA support the view that central H1-stimulation raises the blood pressure. However, the results with dimaprit do not exclude the participation of central H2-receptors in the effect of histamine on the blood pressure.It appears that in the goat the stimulation of central H1- and H2-receptors mediates opposite actions on behaviour. H1-agonist increased and H2-agonist decreased the general activity of the animal.

Effects of osmotic stimuli on vasopressin levels in the CSF of rats.

Arginine-vasopressin (AVP) levels and osmolality were measured in the CSF of rats during 5 days of osmotic stimulation. Dehydration increased AVP levels about 3-fold but did not affect the circadian rhythm of AVP. During dehydration, AVP levels in CSF increased as osmolality increased. Neither AVP levels nor osmolality changed significantly in the CSF of rats receiving 2% NaCl as drinking water. The increased AVP values in CSF may reflect activated release of AVP in the central nervous system during dehydration. Our data also suggest that the AVP release connected with the regulation of osmotic changes may be separate from the mechanism that regulates the circadian rhythm of AVP in the CSF of rats.