Puscas 1 , M. Coltau 1 , L. Gilau 2 , R. Pasca 1 , G. Domuta 1 , M. Baican 3 and A. Hecht 4. Correspondence and Footnotes. Catecholamines released by the sympathetic nervous system and adrenal medulla are involved in regulating a host of physiological functions, particularly the integration of responses to a range of stresses 1. Norepinephrine is the major neurotransmitter in the peripheral sympathetic nervous system, whereas epinephrine is the primary hormone secreted by the adrenal medulla in mammals 2.
Important factors in the response of any cell or organ to sympathomimetic amines are the density and proportion of alpha- and beta-adrenergic receptors 3,4. Studies on DNA cloning have demonstrated the existence of at least nine types of adrenergic receptors 5. Other studies have proved that binding of agonists to these receptors occurs when the catecholamine molecule is in the protonated state 6 , all of these receptors being coupled with G proteins. Carbonic anhydrase CA is a zinc-enzyme discovered by Meldrum and Roughton in which catalyzes the reversible hydration reaction of CO 2 , having a main role in the maintenance of acid-basic equilibrium 7.
Eight isozymes have been described so far, located in the membranes, cytoplasm and mitochondria of all organs. CA I is present both in erythrocytes and in vascular walls and its physiologic role has been incompletely elucidated 8. CA II is to be found both in erythrocytes and in the cytoplasm. The same studies showed that CA I and CA II are activated by nonsteroidal anti-inflammatory drugs 11 and vasodilating prostaglandins and diuretic agents 12,13 inhibit CA while vasoconstrictive prostaglandins activate the enzyme These studies have also demonstrated the involvement of carbonic anhydrase in the regulation of vascular and secretory processes in the organism Our previous work has shown that alpha- and beta-adrenergic agonists activated purified and red cell CA while adrenergic antagonists inhibited CA and reduced the activating effect of agonists on this enzyme 15, In the present investigation we studied the relationship between alpha- and beta-adrenergic agonists and CA activity in vasoconstriction mechanism.
Deisenhofen, Germany , orciprenaline Alupent was purchased from Boehringer Ingelheim, Germany , and noradrenaline and isoprenaline vials were obtained from Sicomed Bucharest, Romania. Erythrocyte studies. We studied the effects of adrenaline, noradrenaline, isoprenaline and orciprenaline on CA I and CA II purified from human erythrocytes.
Kinetic studies were carried out in order to identify the mechanism of action of adrenergic agonists on CA. Maximum reaction rate V max and the Michaelis constant K m were determined. Clinical studies. All patients gave informed consent for a protocol approved by the Ethics Committee of the Center for Research and Medical Assistance in Simleu Silvaniei. We selected 42 healthy male volunteers aged 30 to 50 years and weighing kg, who were randomly divided into three groups.
All subjects resided in the community and were in good general health. Subjects were screened before participation by being submitted to physical examination, a complete blood count, fasting serum glucose, and routine chemistry, urinalysis, and electrocardiogram and their medical history was taken.
Red cell CA I and CA II activity and arterial blood pressure values were determined before and 30 min after drug administration and the blood count, routine chemistry, urinalysis and electrocardiogram were repeated. Vessel studies. In the animal experiments, 20 piglets weighing kg were housed in air-conditioned quarters and had free access to tap water and standard food. Arterial blood pressure was determined 30 min after drug administration and all piglets were sacrificed for isolation of vascular smooth muscle CA I.
CA I activity was determined and compared to that obtained for the control group. Vascular smooth muscle CA I was isolated from the small mesenteric arteries of the animals according to the technique of Lonnerholm et al. CA I and CA II activity was assessed using the stopped-flow method 18 , which consists of measuring the enzymatic activity of CO 2 hydration and is based on a colorimetric method which measures changing pH. The time needed for the pH of the reagent mixture to decrease from its initial value of 7.
The signal transmitted by the photomultiplier from the mixing chamber is received and visualized by a computer equipped with a mathematical coprocessor and the kinetic software package RKBIN IS1. We used p-nitrophenol 0. The CO 2 solution at a concentration of 15 mM as substrate was obtained by bubbling twice-distilled water with CO 2 to saturation.
All reagents were maintained at pH 7. Activity is reported as enzyme units EU per ml. In humans, blood pressure was measured with a standard mercury sphygmomanometer in the classical sitting position and is reported as the mean of three measurements.
When repeated measure ANOVA showed significant differences between groups, the Newman-Keuls multiple comparison test was performed to determine which groups differed significantly. Adrenaline increased CA I activity from 0. Noradrenaline increased CA I activity from 0. Isoprenaline increased CA I activity from 0.
Orciprenaline increased CA I activity from 0. The kinetic data processed according to the Michaelis-Menten equation showed a non-competitive mechanism of action with an increase in V max and a constant K m. Topic Reviews A-Z Save. Alpha Agonists Alpha receptor agonists are substances that activate the sympathetic nervous system by stimulation of alpha receptors, similar to the effects of epinephrine and norepinephrine. Read more about epinephrine. Related Content. The role of the alpha 2 -AR family has long been known to include presynaptic inhibition of neurotransmitter release, diminished sympathetic efferent traffic, vasodilation and vasoconstriction.
This complex response is mediated by one of three subtypes which all uniquely affect blood pressure and blood flow. All three subtypes are present in the brain, kidney, heart and vasculature. However, each differentially influences blood pressure and sympathetic transmission.
0コメント