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J A Ferrendelli

Publications and source records attributed to J A Ferrendelli.

At least 91 records · Page 5Linked to original sources
PubMed1980

Relationships between seizure activity and cyclic nucleotide levels in brain.

The effects of pentylenetetrazol on behavior, EEG activity and regional CNS levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in mice and guinea pigs were studied. Pentylenetetrazol increased cGMP levels in all regions of brain examined (cerebral cortex, hippocampus, striatum and cerebellum) and increased cAMP levels in all regions except striatum. cGMP levels were increased by both sub-convulsant and convulsant doses of pentylenetetrazol. In contrast, cAMP levels were elevated only by concentrations of pentylenetetrazol that produced clinically evident seizures or epileptiform EEG activity. These data indicate that increases in CNS cGMP levels produced by epileptogenic stimuli can occur independently of seizure discharges, whereas accumulation of cAMP requires and is secondary to seizure activity. In conjunction with results of other studies, these data support the hypothesis that cGMP may have a role in seizure genesis and/or propagation, whereas cAMP may be involved in processes that attenuate or terminate seizures.

Animals↗
PubMed1980

The distribution of the components of the cyclic GMP cycle in retina.

Frozen sections of retinas from rabbit (mostly rods), ground squirrel (mostly cones), and monkey (mixed rods and cones) were freeze dried, and samples from all the discrete layers analyzed for the enzymes which form cyclic GMP and subsequently convert it back to GTP. The distribution of cyclic GMP was also measured in monkey retina, and the retinal layers of both monkey and rabbit were analyzed for GTP, GTP plus GDP, ATP, ATP plus ADP, and UTP plus CTP. The ratio of guanylates to adenylates was found to be about 1:1 in photoreceptor cell layers, but only 1:4 or 5 in deeper layers. In all species, guanylate cyclase (EC 4.6.1.2) and cyclic GMP phosphodiesterase were highest in the outer segment layer. Other layers were lower by factors of 10 to 500. Guanylate kinase (EC 2.7.4.8) was extremely high in all photoreceptor cell layers except the outer segments, but was much lower elsewhere. Nucleoside diphosphokinase (EC 2.7.4.6) paralleled guanylate kinase throughout the photoreceptor cell layers, but did not fall to such low levels in the deeper layers of the retina. Although there were significant differences among the three species, they all displayed the same general enzyme pattern.

Adenosine Diphosphate↗
PubMed1980

Regional cortical metabolism in focal ischemia.

Regional cortical levels of organic phosphates and carbohydrates were measured in cat brains, enzymatically inactivated by the technique of "funnel freezing" 1 hour after occlusion of a middle cerebral artery (MCA). Significant metabolic alterations occurred in all hemispheres ipsilateral to the site of occlusion. However, there was marked interindividual variability, with changes ranging from only slight increases in lactate, pyruvate, and adenosine monophosphate (AMP) in small regions of cortex at one extreme, to profound depletion of high-energy phosphates, depression of glucose and pyruvate levels, and increased lactate, adenosine diphosphate (ADP) and AMP levels in much of the hemisphere of the most severely involved animals. In contrast, metabolic changes in the hemisphere contralateral to the site of occlusion were very few or nonexistent. In addition, in all ipsilateral hemispheres there were regions peripheral to the areas of greatest metabolic alteration where there was excessive elevation of glucose levels. The results demonstrate that occlusion of a major cerebral vessel does not produce metabolic changes that are consistent in their distribution or severity. However, the findings of this study probably depict some of the complicated metabolic events that occur clinically during thrombotic or embolic infarction of brain.

Adenosine Diphosphate↗
PubMed1980

Succinimides.

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Animals↗
PubMed1979

beta-Adrenergic regulation of adenosine 3',5'-monophosphate concentration in brain microvessels.

Norepinephrine increases the concentration of adenosine 3',5'-monophosphate (cyclic AMP) in an incubated suspension of brain microvessels. This response can be matched by other drugs that stimulate the beta receptors, but the alpha-adrenergic agonist phenylephrine is without effect; beta-adrenergic blockade abolishes the response while alpha-adrenergic blockade produces no change. The data support the contention that cerebral capillary function is subject to adrenergic neural control.

Adrenergic beta-Agonists↗
PubMed1979

Inhibitory effects of anticonvulsant drugs on cyclic nucleotide accumulation in brain.

Veratridine causes deplorization of excitable cells and produces marked elevation of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) levels in incubated slices of mouse cerebral cortex. Phenytoin, carbamazepine, phenobarbital, primidone, phensuximide, methsuximide, alpha-methyl-alpha-phenylsuccinimide, and high concentrations of clonazepam are anticonvulsant drugs that preferentially prevent maximal electroshock seizures (MES) and generalized tonic-clonic convulsions; all these agents inhibit veratridine-induced accumulation of both cyclic AMP and cyclic GMP. In contrast, ethosuximide, trimethadione, valproic acid, and low concentrations of clonazepam are anticonvulsant drugs that act predominantly against Metrazol and absence seizures; these agents are ineffective or inhibit accumulation of only cyclic GMP. The results suggest that inhibition of cyclic AMP and cyclic GMP accumulation in depolarized brain tissue is a molecular neuropharmacological action characteristic of anticonvulsant drugs that have direct effects on cellular membrane function and prevent MES. Anticonvulsant drugs that do not inhibit accumulation of both cyclic AMP and cyclic GMP in depolarized brain tissue preferentially prevent Metrazol and absence seizures and probably exert their effects by altering neurotransmission mechanisms.

Animals↗
PubMed1979

Effects of reserpine, propranolol, and aminophylline on seizure activity and CNS cyclic nucleotides.

Convulsant doses of pentylenetetrazol (100 mg/kg) increase levels of both cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP in mouse cerebral cortex and hippocampus. In animals pretreated with reserpine, propranolol, or aminophylline, pentylenetetrazol seizures were more severe, cyclic AMP elevations were attenuated or blocked, and cyclic GMP increases were unaffected or augmented. These data indicate that norepinephrine, adenosine, and perhaps other biogenic amines have a regulatory effect on cyclic AMP, but not cyclic GMP, levels in epileptic brain. An increased level of cyclic AMP in brain tissue may have an antiepileptic effect leading to seizure attenuation or termination. By contrast, elevated levels of cyclic GMP may have an epileptogenic effect in initiating or maintaining seizure activity.

Aminophylline↗
PubMed1979

Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties.

Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma.

Adenosine Diphosphate↗
PubMed1978

Calcium and cyclic nucleotide regulation in incubated mouse retinas.

When retinas from dark-adapted C57BL/6 mice were incubated in the dark for 5 min at 37 degrees C in Earle's medium, they contained 80-120 pmol/mg protein of cGMP and about 13 pmol/mg protein of cAMP. When the incubation in darkness was in calcium-deficient Earle's medium with 3 mM EGTA, a 10-20 fold increase occurred in the cGMP level, peaking at 2-3 min, but no change occurred in cAMP. This elevated level fell in 3 min to normal dark levels on return to normal Earle's medium, but was still about three times that of control levels after 15 min in EGTA-containing solution. Bright light after 2 min of dark incubation of dark-adapted retinas resulted in a 40-50% fall in cGMP, and bright light sharply reduced the elevated dark cGMP level of retinas in calcium-deficient media with 3 mM EDTA. However, no depression of normal dark levels of cGMP has thus far been obtained by increasing external calcium levels, even in the presence of the ionophore A23187. All the above phenomena involving dark cGMP levels and calcium are similar in Earle's medium with 100 mM of K+ substituted for Na+. Congenic rodless (rd/rd) mouse retinas have less than 5% of control cGMP and show only traces of calcium sensitivity. Thus, the above phenomena in controls are likely to be largely occurring in rods. The data suggest a dependency of the dark cGMP level on the calcium level, but that the light-induced fall in cGMP may largely be calcium insensitive.

Adaptation, Physiological↗