Effect of calcium channel antagonists in modifying the inhibitory influence of adenosine on insulin secretion.

The present work was performed to study the effect of two calcium channel antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in modifying the inhibitory influence of adenosine on insulin secretion from isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in vivo was also investigated. Both verapamil and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant inhibition of glucose-stimulated insulin secretion from pancreatic islets. Combination of these agents with adenosine 10 mumol/l did not modify the inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent administration of verapamil with adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of adenosine, whereas combined administration of nifedipine and adenosine decreased the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These results may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insulin secretion.

Combined effect of adenosine, alpha adrenergic and adenosine antagonists on serum insulin and insulin secretion from rat pancreatic islets.

1. The effect of adenosine separately or in combination with alpha-1 adrenergic antagonist prazosin and alpha-2 adrenergic antagonist yohimbine as well as adenosine antagonists 8-phenyltheophylline and xanthine amine conjugate on glucose-induced insulin secretion from isolated rat pancreatic islets was studied. 2. Their in vivo effects on serum glucose and insulin levels were also investigated. Adenosine at 10 and 100 microM inhibited significantly, insulin secretion from the isolated islets whereas at 10 mM slightly increased the secretion of insulin. 3. Prazosin used at 100 microM inhibited insulin secretion. When it combined with adenosine (10 microM) it augmented the inhibitory effect of adenosine. 4. In vivo prazosin (21 mg/kg body wt) caused a hyperglycaemia which was accompanied by hypoinsulinaemia. 5. Concurrent administration of this drug with adenosine neither affect the hyperglycaemic nor the hypoinsulinaemic effects of adenosine. 6. On the other hand, yohimbine (100 microM) has no effect neither separately nor in combination with adenosine (10 microM) in modulating the inhibitory effect of adenosine on insulin secretion. 7. When Yohimbine administered at 19.5 mg/kg body wt it did not alter serum glucose but it markedly increased the serum insulin level. Its combined administration with adenosine reduced the hyperglycaemic effect of adenosine with a remarkable increase in serum insulin. 8. Both adenosine-antagonists were ineffective in alteration of insulin secretion. 9. However, combination of 8-phenyltheophylline with adenosine (10 microM) totally blocked the inhibitory effect of adenosine on insulin secretion while xanthine amine conjugate failed to prevent this effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Further studies on prostaglandins. III. Effect of prostaglandins on thyroid activity as assessed by 125I.

The effect of crude prostaglandins extraced from prostate glands of camels as well as that PGE1, on the thyroid activity of male immature Boskat rabbits, was investigated. The iodinated amino acid fractions (T1, T2, T3 and T4) in the serum of the injected groups were determined in control and treated animals. Cytological work on sections of the thyroid glands of the treated and control rabbits were performed to study the effect on subcellular level. The results indicate that both crude and pure prostaglandins have a stimulating effect on thyroid activity. This was indicated by the increased 125I uptake of the thyroids of rabbits and evidenced histologically. PGE1, was found to be more effective as compared with the crude prostaglandins. The indinated amino acid and hormone fractions in the serum of the treated groups showed that T2 was increased as a result of injection of the crude prostaglandins, and T4 was increased after PGE1 injection. Tables and figures explained diversed effect.