A. Casti

Polyamines and noradrenaline following myocardial hypertrophy

Abstract The aliphatic amines, spermine and spermidine, and amino-oxidase activity were evaluated in hypertrophic rabbit heart obtained following aortic arch constriction. The polyamines were determined early after surgery (at 1, 2, 4, 8 h), during the first 10 days (at 1, 2, 5, 6, 10 days) and during the following 6 months (at 1, 2, 4, 6 months) after surgery. The pattern showed a rapid increase of spermine that reached a peak at 5 days after surgery (+146%). The changes of the enzymic activity are in accordance with the behaviour of polyamines. Under the same experimental conditions the myocardial concentrations of noradrenaline were evaluated. This chemical mediator rapidly increased 1 h after aortic stenosis. The results suggest that biogenic amines are related to the metabolic phenomena at the early stages of cardiac hypertrophy, and in particular to protein synthesis.

Polyamine distribution and activity of their biosynthetic enzymes in the European sea bass (Dicentrarchus labrax L.) compared to the rat

1. In the liver, heart and brain of the European sea bass, putrescine concentrations are much higher than in the equivalent rat tissues; spermidine and spermine levels are smaller. 2. Ornithine decarboxylase in the bass liver is more active, but less stable than that in the rat; stability is acquired upon partial purification. Bass liver adenosylmethionine decarboxylase activity is less than that found in the rat. Both are activated and stabilized by putrescine. 4. The activating effect of putrescine decreases as the assay temperature is decreased. This may explain the high level of putrescine but low levels of spermidine and spermine in the bass liver.

A possible role for polyamines in cartilage in the mechanism of calcification

The role of polyamines in cartilage is not known: they may be somehow related to the mechanism of calcification. In epiphyseal cartilage from calf scapulas, they are more concentrated in the ossifying area, where calcification takes place, than in the resting region. Spermidine is present in greater amounts than spermine and putrescine. Since ornithine decarboxylase (EC 4.1.1.17) is measurable only in the resting region of the tissue, it is in this area that polyamine biosynthesis occurs, while they accumulate in the ossifying area. Immunohistochemical evidence is obtained that only in the ossifying zone is spermidine extracellular. It is at this level that the matrix is rearranged to become calcified, and proteoglycans are dissociated and partially removed. The effect of polyamines on solutions of proteoglycan subunits has been studied in vitro by following variations of turbidity and viscosity. While in the presence of putrescine the specific viscosity decreases to asymptotic values, in the presence of either 30 mM spermidine or 2.5-10 mM spermine, the decrement is more marked. At the same concentrations, increase of the turbidity of proteoglycan subunit solutions was observed. Only spermidine showed the capacity of displacing proteoglycan subunits from a column of Sepharose 4B-type II collagen: at 15 mM concentration, about 90% of proteoglycans were removed from the column. Alkaline phosphatase activity, which plays an important role in calcification, is enhanced by spermidine and spermine. These results obtained in vitro support the hypothesis that polyamines may be related to calcification of preosseous cartilage.

Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men

Background  The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion.

Pattern of blood polyamines in healthy subjects from infancy to the adult age

Blood polyamine levels have been determined in 161 healthy subjectsfrom newborn to adult age. During the growth period spermidine and spermine concentrations are always higher than in adulthood. In the first days of life a typical pattern for spermidine and spermine appeared with an early increase in the first hours after birth and a maximum at 24 h; afterwards the levels of both amines gradually and progressively decreased. The levels reached by 10 days of life were mantained until adulthood, at which time a further decrease was evident. The high levels of polyamines during the period of body growth may suggest that also in humans these substances play a role in the process of cellular proliferation.

Effect of spermine on acetylation of histones in rabbit heart.

Abstract Incorporation of [14C]acetate was used as an index of acetylation of histone fractions in rabbit hearts. Spermine (10−6 and 10−5 m ) enhanced acetylation of all histone fractions in myocardial purified nuclei. In perfused hearts, spermine increased acetylation only in arginine-rich histone fractions. During the early stage of myocardial hypertrophy, a condition associated with a rise in the spermine content in the heart, an increased incorporation of [14C]acetate into F2a2 and F2a1 histone fractions was observed. From the results, a possible role of spermine in the mechanism of gene derepression is postulated.

Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Alprazolam (ALP), a benzodiazepine activating GABAergic receptors, is involved in ACTH secretion. WHAT THIS STUDY ADDS • This study demonstrates a partial opioid influence in the inhibitory effect of ALP on the release of ACTH/cortisol during physical exercise. AIMS To establish the possible involvement of alprazolam (ALP) and/or opiates in the mechanism underlying the ACTH/cortisol response to physical exercise. METHODS Tests were carried out under basal conditions (exercise control test), exercise plus ALP (50 µg at time -90 min), naloxone (10 mg at time 0) or ALP plus naloxone. Plasma ACTH and serum cortisol concentrations were evaluated in blood samples taken before, during and after the bicycle ergometer tests. RESULTS ACTH and cortisol concentrations rose significantly after physical exercise. Maximum peak at time 15 min (P ≤ 0.01 vs. baseline) for ACTH and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol. In the presence of naloxone, the ACTH and cortisol responses were significantly increased (maximum peak at time 20 min, P ≤ 0.02 vs. control test for ACTH, and at time 30 min (P ≤ 0.01 vs. baseline) for cortisol) whereas they were abolished by ALP. When ALP and naloxone were given together, the inhibitory effect of ALP was partial. CONCLUSIONS These data demonstrate an inhibitory effect of ALP in the regulation of the ACTH/cortisol response to physical exercise in man and suggest that GABAergic receptor activating benzodiazepines and opioids interact in the neuroendocrine secretion of ACTH/cortisol.

Polyamine biosynthesis in rabbit perfused heart under various degrees of oxygen tension

Abstract Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities increase in hypoxic perfused rabbit heart (more with less severe hypoxia). Anoxic perfusion causes a decrease in the former activity and no effect in the latter. Changes in polyamine specific radioactivity are consistent with those of the the two enzymes, except for the enhancement at 60 minutes of anoxia.

Effect of naloxone on somatostatin inhibition of arginine vasopressin response to physical exercise in normal men

To establish whether somatostatin (SRIH) and/or endogenous opioids play a role in the control of arginine–vasopressin (AVP) response to physical exercise, eight healthy men underwent four bicycle–ergometer tests until exhaustion: exercise control test; exercise plus SRIH, naloxone or SRIH plus naloxone. Serum AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During control test exercise significantly increased serum AVP levels, with a peak value 4.1 times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was significantly reduced by SRIH (AVP peak was only 2.8 times higher than baseline). When SRIH and naloxone were given together, the exercise-induced AVP rise was comparable to that observed in the control test. Results indicate a somatostatinergic involvement in the regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying SRIH inhibitory action, but not in mediation of the AVP response to physical exercise.

Ornithine decarboxylase in perfused rat heart

In the isolated perfused rat hearts, the activity of tissue ornithine decarboxylase gradually decreases over 90 min. In contrast, the activity of S-adenosylmethionine decarboxylase, lactate dehydrogenase, and glutamate-oxalacetate transaminase stays unchanged after a small decrease during the first 10 min. Ornithine decarboxylase is released from the perfused heart under conditions in which neither the lower molecular weight S-adenosylmethionine decarboxylase nor polyamines leak out. Ten minutes of ischaemia did not change the rate of release of ornithine decarboxylase. Ischaemia followed by reperfusion (20 min) increased release of ornithine decarboxylase.