Effects of alpha- and beta-adrenergic stimulation on free magnesium concentrations in platelets from healthy and obese individuals.
We performed this study to investigate whether alpha- and beta-adrenergic agonists are able to regulate intracellular free magnesium concentrations [Mg2+]i in platelets from healthy and obese individuals. Twenty-six informed-consent men (14 healthy and 12 obese) were enrolled in the study. We measured fasting plasma glucose, insulin, epinephrine and norepinephrine. Platelet [Mg2+]i at the baseline and after stimulation with clonidine or isoproterenol was measured by fluorescent probe mag-fura-2. In platelets from healthy subjects, alpha-adrenergic stimulation by clonidine led to a dose-dependent decrease in [Mg2+]i (basal: 245 +/- 39 microM; clonidine 5 pg/mL: 109 +/- 27 microM, p < 0.05; clonidine 10 pg/mL: 77 +/- 26 microM, p < 0.01), while no significant change in platelet [Mg 2+]i was detected in obese men. Furthermore, the co-incubation with clonidine (10 pg/mL) and yohimbine (50-100 pg/mL) completely abated the effect of clonidine on [Mg2+]i in platelets from healthy individuals. Analysis of the time course for platelet magnesium showed that the intracellular magnesium loss induced by clonidine (10 pg/mL) was time-dependent. Conversely, the beta-adrenergic agonist isoproterenol was able to produce a significant rise in [Mg2+]i in platelets from healthy individuals (basal: 234 +/- 40 microM; isoproterenol 2.5 pg/mL: 594 +/- 44 microM, p < 0.05: isoproterenol 5 pg/mL: 681 +/- 56 microM, p < 0.01), while no such finding was detectable in platelets from obese patients. When platelets from healthy subjects were co-stimulated with isoproterenol (5 pg/mL) and propranolol (10-20 pg/mL), the ionophoric effect of the beta-adrenergic agonist was completely reverted. The time course of isoproterenol (5 pg/mL) effect on platelet [Mg2+]i showed that the ionophoric effect of isoproterenol was time-dependent. In conclusion, (1) the stimulation of alpha-adrenergic receptor by clonidine is able to induce a significant dose- and time-dependent fall in platelet [Mg2+]i; (2) the stimulation of beta-adrenoceptors by isoproterenol lead to a signifcant time- and dose-dependent rise in platelet [Mg2+]; (3) the ionic effect of alpha- and beta-adrenergic stimulation is not detectable in obese subjects, in whom is probably present a reduced sensitivity to the ionic effect of adrenergic agonists.
Malara
A
A
Department of Internal Medicine, Policlinico Universitario, University of Messina, Italy.
Corsonello
A
A
Buemi
M
M
De Domenico
D
D
Ientile
R
R
Corica
F
F
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000097:blood*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000188:drug therapy; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D007328:Insulin; D015016:Yohimbine; D008274:Magnesium; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine