SUMMARY1. The catecholamines adrenaline (A), noradrenaline (NA) and dopamine (DA) were determined in plasma samples of man and various animal species using a highly sensitive radioenzymatic method.2

The content of adrenaline (Ad), noradrenaline (NA) and dopamine was measured in human, guinea‐pig, cat, rabbit and rat blood platelets by a highly sensitive and specific radioenzymatic method. In all platelet specimens analyzed, the content of the three catecholamines (CA) was several thousand times lower than that of 5‐hydroxytryptamine (5‐HT). In basal conditions, the NA concentration in platelets and plasma always exceeded that of Ad and dopamine. In rat and rabbit platelets, Ad, NA and dopamine were present only in the free (unconjugated) form. Platelets of rats with storage pool deficiency (Fawn‐hooded) contained much less 5‐HT and CA than normal rat platelets. Following restraint stress, platelets of Fawn‐hooded rats, in contrast to normal rat platelets, did not accumulate CA in spite of a dramatic rise in plasma CA. Reserpine, a monoamine depletor, released CA as well as 5‐HT from rabbit platelets in vivo. Subcellular fractionation experiments with rabbit platelets indicate that both CA and 5‐HT are most concentrated in the fraction consisting of pure 5‐HT organelles. Both in humans and rabbits the concentration gradient between platelets and plasma was much lower for CA than for 5‐HT, indicating that a high affinity transport mechanism operates in vivo for 5‐HT but not for CA. In conclusion, the present data show that both human and animal platelets contain Ad, NA and dopamine. The bulk of the CA seems to be stored as unconjugated amines together with 5‐HT, histamine and p‐octopamine in a multitransmitter storage site, namely the 5‐HT organelle.

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We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

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Oestrogens are the key factor in the sexual differentiation of the mammalian brain and play an important role in the activity of selected areas of the mature brain. To pursue the study of oestrogen action on neural cells at the molecular level, we developed a human neuroblastoma cell line (SK-ER3) expressing the oestrogen receptor (ER). Treatment of these cells with 17beta-oestradiol causes growth arrest and morphological and biochemical differentiation. The aim of the present study was to investigate whether oestrogen-differentiated SK-ER3 neuroblastoma cells acquire the ability to synthesize a specific neurotransmitter and whether the growth arrest previously reported can be ascribed to the blockage of the cells at a specific stage of the cell cycle. The results presented here indicate that oestrogens induce accumulation of SK-ER3 cells in the G0 phase of the cell cycle, underscoring the acquisition of a mature neural phenotype upon hormonal treatment. Most importantly, we show that in the differentiated cells the content of tyrosine hydroxylase and Na+-dependent dopamine uptake is significantly augmented, proving that the oestrogen-differentiated SK-ER3 cells can synthesize and store a specific neurotransmitter. In addition, we prove that the dopamine accumulated in differentiated SK-ER3 cells can be released. These studies therefore suggest that oestrogen treatment results in the acquisition of a fully functional dopaminergic phenotype of SK-ER3 cells. Ample evidence shows a link between dopaminergic neurons and oestrogen activity in hypothalamic and non-hypothalamic areas of the mammalian brain. Our study indicates that oestrogens might play a primary role in committing undifferentiated neuroblasts towards the dopaminergic phenotype.