cyclic-gmp and 2-aminoisobutyric-acid

This study was performed to test the hypothesis that a direct application of cyclic guanosine monophosphate (cGMP) to the cortex would increase blood-brain barrier (BBB) permeability. Rats were anesthetized with 1.4% isoflurane and were mechanically ventilated. Two cranial windows (3 mm in diameter) were made on each side of the rat's skull (a total of four windows on each rat) to expose the cerebral cortex. A patch of normal saline, 10(-5) M, 10(-4) M, or 10(-3) M 8-bromo-cGMP was applied to each cranial window. The patches were changed every 5 min. Ten minutes after applying the patches, BBB permeability was determined by measuring the transfer coefficient (Ki) of [alpha-14C]aminoisobutyric acid. Vital signs were not changed after applying 8-bromo-cGMP. Blood gases were within normal limits. In the cortex, 10(-5) M 8-bromo-cGMP did not significantly affect the Ki; 10(-4) M 8-bromo-cGMP increased the Ki by 115%; 10(-3) M 8-bromo-cGMP increased the Ki by 124%. However, there was no statistical difference in the Ki between the doses of 10(-4) M and 10(-3) M 8-bromo-cGMP. In the pons where no patch was applied, the Ki was similar to that of the cortical area where a normal saline patch was applied. Our data demonstrated that a direct application of cGMP to the cerebral cortex significantly increased the permeability of the BBB.

Topics: Aminoisobutyric Acids; Animals; Blood-Brain Barrier; Cerebral Cortex; Cyclic GMP; Dose-Response Relationship, Drug; Excitatory Amino Acids; Hemodynamics; Microcirculation; Nitric Oxide; Pons; Rats; Second Messenger Systems; Stimulation, Chemical

The characteristics of interaction of insulin with specific receptors on exocrine pancreatic cells of the guinea pig have been studied. Insulins from different species as well as certain insulin analogs were found to have affinities to receptors on pancreatic acinar cells which are similar to what have been described for insulin receptors in other organs of different mammalian species. Binding was rapid and reversible at 37 C but dissociation was markedly slower at 12 C. Clear indications of negative cooperativity between binding sites were not seen. Bovine and chicken insulin bound with approximately a 100-fold higher affinity to guinea pig insulin receptors than guinea pig insulin itself. The number of insulin receptors per acinar cell were comparable with what has been described for other mammalian cells. Part of cell-associated insulin was internalized. After 60 min of incubation the major part of radioactivity in the incubation medium as well as in cells appeared as intact [125I] iodoinsulin on a Sephadex G-50 column and less than 12% of radioactivity was eluted as breakdown products together with Na 125I.

Topics: Aminoisobutyric Acids; Animals; Binding, Competitive; Cattle; Chickens; Cyclic AMP; Cyclic GMP; Glucose; Guinea Pigs; Insulin; Leucine; Male; Pancreas; Proinsulin; Receptor, Insulin; Swine; Time Factors