Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) in rat model of non-insulin-dependent-diabetes.

Effect of chronic treatment with Bis(maltolato)oxovanadium (IV) (BMOV) was studied in streptozotocin (STZ)-induced neonatal non-insulin-dependent-diabetic (NIDDM) rats. Intraperitoneal injection of STZ (90 mg kg(-1)) in Wistar rat pups (day 2 old) produced mild hyperglycemia, impaired glucose tolerance and insulin resistance at the age of 3 months. Treatment with BMOV (0.23 mM kg(-1)) in drinking water for 6 weeks produced a significant decrease in elevated serum glucose levels without any significant change in serum insulin levels in diabetic rats. BMOV treatment significantly decreased integrated area under the glucose curve without any significant change in integrated area under the insulin curve indicating improved glucose tolerance. Treatment also significantly increased K(ITT) value of diabetic rats indicating increased insulin sensitivity. BMOV treatment significantly reduced hypercholesterolemia in diabetic rats. Treatment also significantly decreased serum triglyceride levels in both diabetic and non-diabetic rats. The data suggest that chronic BMOV treatment improves glucose and lipid homeostasis. These effects appear to be due to the insulin sensitizing action of vanadium.

Nitric oxide: a molecule of the millennium.

Recognition of Nitric oxide (NO) as the chemical entity of endothelium-derived relaxing factor (EDRF) has renewed the interest of the scientific community in the last decade. The outcome of research the world over is that the dreaded environmental pollutant is found to be a fundamental physiological mediator and effector. NO is synthesized endogenously by enzymes nitric oxide synthase (NOS) in specialized tissues from its precursor L-arginine. The L-arginine-NO biosynthetic pathway is involved in physiological processes such as vasodilation, memory, neuroprotection, peristalsis, penile erection, immune defense, various endocrine and exocrine secretions in various systems such as cardiovascular, CNS, reproductive and immune system. Small quantities of NO produced by constitutive enzymes mediate these physiological effects. The expression of inducible enzyme or overstimulation of constitutive enzymes leading to production of large quantities of NO is implicated in the cytotoxic effects observed in various disorders like AIDS, cancer, Alzheimer's, arthritis etc. In conclusion, NO is a 'double edged sword' and the challenge before the scientific community is to develop strategies for using it to our advantage.

Involvement of K+ channels in the relaxant responses to various agonists in estrogen primed rat uterus.

The present investigation was undertaken to study the effects of K+ channel openers in the relaxant responses to various agonists in estrogen primed rat uterus. Adrenaline and isoprenaline produced a dose-dependent relaxation in the estrogen primed rat uterus. The relaxant responses were found to be significantly potentiated when the preparations were exposed to PSS devoid of calcium. The responses to isoprenaline were found to be greater in the preparations depolarized with 40 mM KCl instead of 80 mM KCl. KCl failed to produce any contractile effect in the presence of D-600. Further, the addition of D-600 completely relaxed the KCl depolarized rat uterus. Pinacidil and cromakalim failed to relax 80 mM KCl depolarized rat uterus. However, they produced dose-dependent relaxation in the preparations depolarized with 40 mM KCl. The relaxant responses to pinacidil and cromakalim were competitively blocked by procaine. However, they were not altered by either propranolol or cimetidine. The relaxant responses to isoprenaline and histamine were found to be potentiated by pinacidil and cromakalim. These results indicate that in rat uterus in addition to adenylate cyclase c-AMP, potassium channels are also involved in the relaxant responses to isoprenaline and histamine.

Evidence for catecholamine-depleting action of fluoxetine.

The present investigation was undertaken to study the interaction of fluoxetine with 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in rat anococcygeus muscle and vas-deferens. In rat anococcygeus muscle responses to NA were significantly potentiated after 30 min and 60 min incubation with fluoxetine (2.9 x 10(-9) M). The responses to 5-HT were however, inhibited after 30 min incubation with fluoxetine in this preparation. On rat vas-deferens also, the responses to NA were potentiated after 30 min incubation with fluoxetine. The response to 5-HT were not altered significantly. In rats pretreated with fluoxetine (5 mg/kg, ip) for seven days, the responses to NA were significantly potentiated in rat anococcygeus muscle. Whereas the responses to 5-HT and tyramine were significantly inhibited. The inhibited responses to 5-HT restored back to normal when the anococcygeus muscle was pre-incubated with NA for 30 min.

Autoinhibition and desensitization of serotonergic responses in guinea pig ileum.

The present study was undertaken to investigate the autoinhibition and desensitization of 5-hydroxytryptamine (5-HT) using another agonist MK-212 on guinea pig ileum. 5-HT and MK-212 produced dose dependent contractions of guinea pig ileum. The responses to MK-212 were reduced in the presence of 5-HT and vice versa. Neither 5-HT nor MK-212 produced any change in the responses to histamine, acetylcholine or KCl. Increase in Ca++ in bathing fluid reversed the desensitization produced by MK-212 or 5-HT. Our data suggest that 5-HT and MK-212 produce desensitization which is specific for serotonergic receptors and possibly involves Ca++ ions.