Differential changes in alpha- and beta-adrenoceptor linked [45Ca2+] uptake in platelets from patients with anorexia nervosa.
[45Ca2+] Uptake was studied in response to adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP in platelets from patients with anorexia nervosa. In both controls and anorectics, adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP stimulated [45Ca2+] uptake. In receptor subtype characterisation studies on control platelets, adrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine (an alpha 2-adrenoceptor antagonist) and the specific beta 2-adrenoceptor antagonist ICI 118,551, but not by atenolol (a beta 1-antagonist). Isoprenaline action was blocked by ICI 118,551, but not by yohimbine. Noradrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine but not by ICI 118,551. In platelets from anorectic patients, there was a significant increase in noradrenaline-stimulated [45Ca2+] uptake, a significant diminution in adrenaline and isoprenaline-stimulated [45Ca2+] uptake, but no significant difference in (Bu)2cAMP-stimulated [45Ca2+] uptake, when compared with controls. Basal uptake was also significantly enhanced in anorectics and was found to be inhibited with verapamil but not adrenoceptor antagonist. These data firstly indicate that both alpha 2- and beta 2-adrenoceptor activation elicits [45Ca2+] uptake by platelets. It is proposed that this stimulated [45Ca2+] uptake does not reflect changes in cytosolic Ca2+ but to localized changes of Ca2+ at the plasma membrane, possibly associated with receptor activation, per se. The respective increase and decrease of alpha- and beta-adrenoceptor activity in platelets from anorectic patients is in accord with other reports of changes of adrenoceptor number and type in platelets and other cells from anorectic patients. There may also be an increase in calcium channel activity in platelets from anorectics.
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, England.
J
J
Gill
V
V
DeSouza
A
A
Wakeling
P
P
Dandona
J Y
JY
Jeremy
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood*; D001262:Atenolol / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002132:Calcium Radioisotopes; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D015016:Yohimbine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002132:Calcium Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; C026777:ICI 118551; D001262:Atenolol; D003994:Bucladesine; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine