PubMed Health⌕ Search

Biomedical subjects

T Mäki

Publications and source records attributed to T Mäki.

28 records · Page 2Linked to original sources
PubMed1990

Reduction of lymphocytic beta-adrenoceptor level in chronic alcoholics and rapid reversal after ethanol withdrawal.

Plasma catecholamine levels, lymphocytic beta-adrenoceptor densities and lymphocytic cAMP production were studied in 10 male subjects attending a withdrawal clinic after prolonged alcohol abuse. On admission the mean beta-adrenoceptor density was 29 +/- 9 fmol mg-1 protein (about 60% of the mean level of healthy control subjects, P less than 0.002). The following day a significant elevation of the beta-adrenoceptor level up to 46 +/- 19 fmol mg-1 protein (P less than 0.05) took place. This was accompanied by a parallel activation of the beta-adrenoceptor-mediated cAMP production of the lymphocytes. No major changes in beta-adrenoceptor levels or cAMP production took place during the next 7 days. Plasma catecholamine levels were elevated at arrival and decreased steadily during the withdrawal period. In conclusion, chronic alcoholism is associated with a reduction of lymphocytic beta-adrenoceptor density and functioning, which is followed by a rapid reversal during abrupt ethanol withdrawal. Thus an accelerated responsiveness to catecholamines may occur during the first ethanol-free day of chronic alcoholics.

Adult↗
PubMed1990

The beta-adrenergic system in man: physiological and pathophysiological response. Regulation of receptor density and functioning.

Catecholamines play an essential role in the activation of the cardiovascular system and in the regulation of energy metabolism in a variety of physiological conditions. Many of these effects are mediated through beta-adrenoceptors located on cell membranes. Binding of catecholamines to beta-adrenoceptor increases the concentration of intracellular cyclic AMP which in turn activates protein kinase A. This enzyme phosphorylates a number of other intracellular enzymes influencing cell metabolism and functions. The primary structures of the receptor and its topography in the cell membrane as well as its binding domains have been partially clarified. In studies of the human beta-adrenergic receptors blood lymphocytes have mostly been used as model cells. These cells carry receptors of mainly the beta 2-subtype. The adequacy of this model system has been demonstrated in several studies. In clinical work receptor assays have had limited use until now. However, studies on the pathophysiology of the adrenergic system in several diseases have revealed that receptor alterations may constitute an important factor in the disease process. Measurements of adrenergic receptors may also have increasing usefulness in determining optimal drug concentrations. Our own studies have primarily focused on physiological adjustments in the beta-adrenergic system during acute or prolonged physical exercise as well as receptor changes in heart failure, muscle diseases and the alcohol withdrawal syndrome. We have also explored receptor dynamics during therapy with beta-blocking agents. These studies, briefly reviewed in this communication, have led to the following conclusions: (1) High aerobic capacity is associated with an increased density and ability of lymphocytic beta-adrenoceptors to respond to catecholamines. (2) Both short-and long-term physical exercise induce a rapid up-regulation and more effective functioning of lymphocytic beta-adrenoceptors. (3) Administration of beta-blocking drugs is associated with a subnormal exercise-induced up-regulation and decreased functioning of the lymphocytic beta-adrenoceptors. (4) The exercise-provoked up-regulation and improved functioning of beta-adrenoceptors is blunted in heart failure patients. (5) Patients with Duchenne-type of muscular dystrophy have a reduced number of lymphocytic beta-adrenoceptors. (6) In chronic alcoholics the lymphocytic beta-adrenoceptor level is subnormal but during abrupt ethanol withdrawal a rapid increase in the number and functioning of the receptors to a normal level takes place. This sequence of events may lead to a condition of relative adrenergic hypersensitivity.

Adrenal Gland Neoplasms↗
PubMed1989

Response of the beta-adrenergic system to maximal dynamic exercise in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

In congestive heart failure (CHF), prolonged exposure to high plasma catecholamine levels may reduce the responsiveness of the adrenergic system to physiologic stimuli. In healthy subjects, exercise is known to induce a rapid up-regulation of lymphocytic beta adrenoceptors. Lymphocytic beta-adrenoceptor density, lymphocytic basal and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) response, plasma catecholamine concentrations and plasma cAMP levels were studied during maximal ergometer exercise in 11 patients with CHF secondary to dilated cardiomyopathy and in 6 healthy control subjects. At rest, there was no difference in the lymphocytic beta-adrenoceptor levels between the patients and control subjects (48 +/- 3 vs 42 +/- 5 fmol/mg protein, respectively). However, the exercise-induced increase in lymphocytic beta adrenoceptors was attenuated in patients when compared with controls (26 +/- 6 fmol/mg protein [56%] vs 75 +/- 16 fmol/mg protein [204%], respectively, p less than 0.02). A subgroup of 4 patients with the lowest exercise capacity (peak oxygen uptake less than 12.5 ml/min/kg) had even more reduced up-regulation compared with the other 7 patients (13 +/- 1 fmol/mg protein [29%] vs 34 +/- 9 fmol/mg protein [71%], p less than 0.05). The lymphocytic cAMP response at rest and during exercise tended to be lower in patients compared with controls, but the differences did not reach statistical significance. The plasma levels of epinephrine and norepinephrine at rest were higher in patients compared with controls, but no difference was found in the exercise values. The plasma levels of cAMP correlated closely with plasma catecholamine levels at rest, but not during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Lymphocytic beta-adrenergic receptors in X-linked muscular dystrophy.

Lymphocytic beta-adrenoceptor levels, receptor binding affinity, lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and plasma catecholamine levels were studied in 49 patients with neuromuscular diseases and in 10 healthy subjects. Patients with X-linked muscular dystrophy (Duchenne, 13 patients; Becker, 4 patients) showed a significant reduction in lymphocytic beta-adrenoceptor densities (35.9 +/- 2.2 fmol/mg protein vs. 49.6 +/- 3.6 fmol/mg, controls; P less than 0.02), whereas the receptor levels for the patients with spinal muscular atrophy (15), polymyositis (10) and for Duchenne carriers (7) did not differ significantly from the corresponding levels for the control subjects. The reduction in the beta-adrenoceptor density was not correlated with the physical disability of the patients. Lymphocytic beta-adrenoceptor affinity (KD) and basal and isoproterenol-stimulated cAMP levels were all comparable to control subjects' values. Catecholamine levels showed mild inconsistent elevations in various patient groups. The results suggest that reduction in cellular beta-adrenoceptors is characteristic of X-linked muscular dystrophies. Its relationship to the basic gene defect is unknown.

Adolescent↗
PubMed1989

Effect of acute ethanol intake and hangover on the levels of plasma and urinary catecholamines and lymphocytic beta-adrenergic receptors.

To determine whether acute ethanol administration affects the function of the adrenergic system the concentrations of plasma catecholamines and cyclic AMP (cAMP), the level of lymphocytic beta-receptors, the concentration of basal and isoproterenol-stimulated lymphocytic cAMP and the excretion of urinary catecholamine metabolites were studied in six healthy men. These parameters were also measured during the hangover, both under resting condition and during an anaerobic ergometer exercise. Acute intake of ethanol (1.5 g/kg body weight) had no statistically significant effect either on plasma adrenaline and noradrenaline concentrations or beta-adrenergic receptor levels. Ethanol consumption did neither change the urinary excretion of catecholamine metabolites (homovanillic acid, normetanephrine, metanephrine, and 3-methoxyhydroxymandelic acid). Exercise was associated with a 6-10-fold elevation in plasma adrenaline and noradrenaline concentrations and with a two- to threefold elevation on beta-adrenergic receptor levels. This effect of exercise was not modified by preceding alcohol intake and resulting hangover. These preliminary findings suggest that acute alcohol intake does not significantly alter the concentration and functioning of human beta-adrenergic receptors.

Adult↗
PubMed1989

Density and functioning of human lymphocytic beta-adrenergic receptors during prolonged physical exercise.

In order to study the regulation of beta-adrenergic receptor number and function in response to prolonged physical effort, lymphocytic beta-adrenoceptor density (determined by (-)[125I]iodocyanopindolol binding), lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and concentrations of plasma catecholamines were measured before and during 3 h running exercise in eight healthy volunteers. A significant (P less than 0.01) increase of the lymphocytic beta-adrenoceptor density from 45 +/- 4 to 81 +/- 9 fmol mg-1 protein (mean +/- SEM) took place during the first hour of exercise. As the exercise was continued for up to 2.1-3 h, the receptor densities did not change significantly any more and remained elevated (72 +/- 9 fmol mg-1 protein) in comparison to the resting levels (P less than 0.02). The isoproterenol-stimulated cAMP production of the lymphocytes increased during the first hour of running from 190 +/- 36 to 269 +/- 56 pmol mg-1 protein (P less than 0.01) and returned to the resting level at the end of the exercise (182 +/- 38 pmol mg-1 protein). The mean levels of plasma catecholamines increased approximately sixfold during the first hour of exercise and remained elevated until the end of the running. This study demonstrates that the beta-adrenergic receptor system is activated in lymphocytes during prolonged aerobic physical exercise. This activated state becomes, however, attenuated within 2-3 h of exercise as indicated by a diminishing ability of beta-adrenoceptors to mediate catecholamine-induced cAMP production.

Adult↗
PubMed1988

Propranolol attenuates exercise-induced increment in human lymphocytic beta-adrenergic receptors.

The effect of peroral propranolol administration on the level of lymphocytic beta-adrenergic receptors was studied in six healthy volunteers using an acute exercise test. When no drug was used, a 15-min ergometer exercise period induced a significant increase in the receptor density (from 42 +/- 5 to 117 +/- 14 fmol/mg protein; mean +/- SEM), followed by a return to the pre-exercise level after a 1-hr rest. During propranolol administration (40 mg, three times daily), the basal receptor level (49 +/- 4 fmol/mg protein) did not change but the exercise-induced increment of the receptor density was significantly inhibited (peak value 79 +/- 5 fmol/mg protein, p less than 0.05). This effect could not be explained by direct competition for receptor binding sites by propranolol nor by differences in the plasma adrenalin and noradrenaline concentrations during the two tests. The fact that propranolol interferes with the normal adaptation of the beta-adrenergic receptor level to acute exercise may explain some of the adverse effects of beta-blocking drugs on physical performance.

Adult↗
PubMed1987

Beta-adrenergic receptors of human lymphocytes in physically active and immobilized subjects: characterization by a polyethylene glycol precipitation assay.

To investigate the role of physical conditioning in the regulation of cellular beta-adrenergic responsiveness in man, a simple and accurate method for the determination of lymphocytic beta-adrenergic receptors was developed and subsequently utilized for the characterization of these receptors in subjects with varying degrees of physical fitness. This method combines the advantages of the use of [125I]iodocyanopindolol as the radioligand and polyethylene glycol (PEG) precipitation for the separation of bound and unbound radioligand. The assay is quick and easy to perform and allows several samples to be processed simultaneously. The concentration of beta-adrenergic receptors in lymphocytic membrane particulates in 16 healthy subjects was 58 +/- 4 fmol/mg protein (mean +/- SEM) and the Kd of the interaction between [125I]iodocyanopindolol and the receptor was 4 X 10(-11) mol/l. The receptor level was similar in both sexes. As compared with the controls, the cellular concentration of beta-adrenergic receptors was higher in eight regularly competing long-distance runners (73 +/- 4 fmol/mg protein; p less than 0.025), whereas the corresponding receptor level in six sprinters (62 +/- 9 fmol/mg protein) did not differ from that of controls. The concentration of lymphocyte beta-adrenergic receptors in seven patients undergoing supine immobilization for weeks because of neck fracture or dislocation showed a wide range from 44 to 155 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Role of acetaldehyde in the induction of heart left ventricular atrial natriuretic peptide gene expression in rats.

We studied the effects of ethanol and acetaldehyde on myocardial gene expression of atrial natriuretic peptide (ANP) and growth of rats. Combined ethanol and calcium carbimide treatment increased blood-acetaldehyde levels and ANP mRNA levels by 40-60% in 2-8 day experiments, compared to the controls. The results suggest a role for acetaldehyde in the development of alcoholic heart dysfunction.

Acetaldehyde↗