The calcium ionophore A23187 stimulates glycoprotein secretion by the guinea pig gallbladder.

The purpose of this study was to examine the role of calcium ions in gallbladder glycoprotein secretion in cultured guinea pig gallbladder explants. The calcium ionophore A23187 showed a threshold of 2 micrograms per ml medium for stimulation of secretion of [3H]glucosamine-labeled glycoproteins over a 30 min incubation period. The ionophore at 3 and 5 micrograms per ml medium resulted in a 3- to 4-fold increase in secretion of [3H]glucosamine-labeled glycoproteins. Ionophore-induced stimulation of glycoprotein secretion was abolished by the addition of 0.01 mM verapamil to the medium. To study the effect of changes in extracellular calcium on basal glycoprotein secretion, explants were cultured for 24 hr in media with 0.007, 0.5 or 2.0 mM calcium; no differences in basal glycoprotein secretion were observed. When cultured in medium with 1.0 mM EGTA, basal secretion decreased significantly vs. controls in 0.007 mM total calcium medium. Total [3H]glucosamine incorporation by explants in medium with EGTA was unaltered, however, suggesting that the low level of calcium in the medium was selectively impairing the secretory process. These findings indicate that calcium ions are important in the regulation of gallbladder glycoprotein secretion.

Metabolic effects of acarbose administration in normal and diabetic rats.

The effect of acarbose on cardiac and hepatic metabolism was investigated in normal and diabetic rats. Groups of rats were fed one of the three following diets for 7 days: (1) ground Purina chow, (2) ground Purina chow fortified with raw corn starch and sucrose, and (3) the above high carbohydrate diet, with added acarbose (40 mg/100 g food). At the end of the dietary period the rats were decapitated, and a sample of liver tissue was removed and frozen in liquid nitrogen. The heart was extirpated for subsequent perfusion by the Langendorff technique. Increases in liver and heart glycogen produced by the high carbohydrate diet in the normal rats were prevented completely when acarbose was incorporated into the food. In diabetic animals, liver glycogen was uniformly lower than normal, irrespective of the diet or the presence of acarbose. With animals fed the control diet, cardiac glycogen was higher in diabetic than in normal rats. The high carbohydrate diet caused a lowering of heart glycogen in diabetic rats and this reduction in glycogen content was reversed by including acarbose in the diet. Effects of isoproterenol on myocardial phosphorylase a activity were determined in hearts from normal and diabetic rats given one of the three diets. The high carbohydrate diet decreased the enzymatic response to the catecholamine in hearts from both normal and diabetic animals, and this phenomenon was prevented by the presence of acarbose in the diet. In diabetic rats fed any of the three diets, the activation of cardiac phosphorylase by isoproterenol was greatly accentuated. Measurements of heart uridine kinase showed that the activity of this enzyme was lower than normal in hearts from diabetic rats given either the control or the high carbohydrate diet. The presence of acarbose in the latter diet resulted in a significant decrease in cardiac uridine kinase activity in hearts from normal rats. The results of this study demonstrate the effectiveness of acarbose in modulating tissue metabolism in normal and diabetic animals.

Interaction between thyroxine and tricyclic antidepressant drugs on cardiac neurotransmitter receptors.

The effect of chronic administration of desmethylimipramine (DMI) and iprindole on cardiac neurotransmitter receptors was studied. In addition, the influence of these drugs on the action of thyroxine (T4) on myocardial receptors was investigated. Administration of iprindole (10 mg/kg i.p., twice daily for 11 days) markedly increased the number of beta- adrenergic receptors in the heart and significantly reduced the affinity of these receptors for (-)[3H]dihydroalprenolol ([3H]DHA). Injection of T4 (500 mg/rat i.m., for 5 days) concomitantly with iprindole resulted in a lower beta-adrenergic receptor density that with iprindole treatment alone, but significantly higher than that measured in control rats. Affinity of the receptors for (-)[3H]quinuclidinyl benzilate ([3H]QNB) in heart membrane preparations of animals pretreated with T4 alone or with T4 plus iprindole was not different from control. Neither pretreatment with DMI nor with iprindole affected the density of cholinergic muscarinic receptors in the heart or their affinity for [3H]QNB. The decrease in cardiac cholinergic receptors induced by administration of T4 was not prevented by simultaneous injections of DMI. Combined administration of iprindole and T4 caused a reduction in the affinity of myocardial cholinergic muscarinic receptors, but restored the number of these receptors to normal. The results demonstrate distinct differences between DMI and iprindole in their effects on cardiac neurotransmitter receptors and in the influence of these drugs on the actions of T4 on receptors in the heart.