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Biomedical subjects

R A Barraco

Publications and source records attributed to R A Barraco.

At least 55 records · Page 3Linked to original sources

A possible role of endogenous adenosine in the sedative action of meprobamate.

The behavioral interaction of intraperitoneal (i.p.) injections of meprobamate with intracerebroventricular (i.c.v.) injections of adenosine or 5'-N-ethylcarboxamidoadenosine (NECA) was examined on spontaneous locomotor activity in mice. The locomotor depressant effect of meprobamate, an adenosine uptake inhibitor, was potentiated by adenosine, but not by NECA, an uptake-resistant adenosine analogue. These findings suggest that heightened endogenous adenosine levels could mediate some of the central actions of meprobamate.

Adenosine↗

Behavioral interaction of adenosine and trifluoperazine in mice.

Mice were implanted with chronic indwelling cannulae in the lateral cerebral ventricle. A dose-response curve was established for the effect of i.p. injections of trifluoperazine (TFP) on spontaneous locomotor activity. In addition, the behavioral interaction of i.p. injections of TFP with intracerebroventricular (i.c.v.) injections of adenosine (ADO) was examined. TFP depressed locomotor activity in a dose-dependent manner. A dose of ADO, which had no effect on locomotor activity when given alone, enhanced the depressant effects of TFP at all doses. As a control for the specificity of this behavioral interaction, mice also were given i.p. injections of TFP in combination with i.c.v. injections of 5'-N-ethylcarboxamidoadenosine (NECA), an uptake-resistant adenosine analogue. TFP and NECA did not interact to produce a significantly more pronounced locomotor depression. These results substantiate the notion that the sedative actions of TFP involve the inhibition of adenosine uptake and thus potentiation of extracellular adenosine levels.

Adenosine↗

Depressant effect of forskolin on spontaneous locomotor activity in mice.

Forskolin, an activator of adenylate cyclase, depressed spontaneous locomotor activity when injected intracerebroventricularly into mice in doses of 10 and 100 micrograms. The findings suggest that increases in brain cAMP levels may be associated with a reduction in excitability.

Adenylyl Cyclases↗

Behavioral interaction of adenosine and diazepam in mice.

Mice were implanted with chronic indwelling cannulae in the lateral cerebral ventricle. The behavioral interaction of intraperitoneal (i.p.) injections of diazepam with intracerebroventricular (i.c.v.t.) injections of adenosine or 5'-N-ethylcarboxamidoadenosine (NECA) was examined on spontaneous locomotor activity. Concurrent injections of i.c.v.t. adenosine and i.p. diazepam, at doses which had no significant effect on locomotor activity when given alone, acted synergistically to produce a marked depression of locomotor activity. In contrast, i.p. injections of diazepam did not potentiate the locomotor depressant effects of i.c.v.t. injections of NECA, an uptake resistant analog of adenosine. These findings support the possibility of specific benzodiazepine-adenosine interactions in the central nervous system.

Adenosine↗

Dissociation of the locomotor and hypotensive effects of adenosine analogues in the rat.

Rats implanted with chronic indwelling cannulae were injected in the lateral cerebral ventricle with two adenosine analogues and the effects on spontaneous locomotor activity and blood pressure recorded. Both analogues produced dose-related decreases in locomotor activity, with 5'-N-ethylcarboxamidoadenosine (NECA) exhibiting slightly more potent depressant activity than (-)-N-(1-methyl-2-phenylethyl)adenosine (L-phenylisopropyladenosine) (L-PIA). NECA and L-PIA also produced dose-related reductions in blood pressure but the threshold dose for hypotensive activity was 10-100-fold higher than the dose required for depression of spontaneous locomotor activity. The depression of locomotor activity and the hypotensive effect of both analogues were antagonized by parenteral injections of caffeine. These results show that the hypoactive and hypotensive effects of adenosine analogues can be dissociated and that methylxanthines probably exert an antagonism of central adenosine receptors in the rat.

Adenosine↗

Behavioral interaction of adenosine and methylxanthines on central purinergic systems.

Mice implanted with chronic indwelling cannulae were injected in the lateral cerebral ventricle with adenosine (ADO); an adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA); a potent adenosine uptake inhibitor, papaverine (PAP); and a methylxanthine, 3-isobutyl-1-methylxanthine (IBMX). All drugs produced dose-related decreases in spontaneous locomotor activity and the order of potency for locomotor depression was: NECA much greater than IBMX greater than ADO, PAP. Further, the behavioral interaction of i.p. injections of caffeine with drug-induced locomotor depression was examined at a dose of caffeine which had no effect on locomotor activity when given alone. Caffeine antagonized the depressant effects of NECA at all doses. However, doses of IBMX producing only behavioral depression, in combination with caffeine, elicited pronounced behavioral stimulation. At higher doses of ADO and PAP, caffeine antagonized their depressant effects whereas at the lower doses of ADO and PAP in combination with caffeine there was behavioral stimulation. These results suggest there is a complex behavioral interaction between methylxanthines and central purinergic systems.

1-Methyl-3-isobutylxanthine↗

Anticonvulsant effects of adenosine analogues on amygdaloid-kindled seizures in rats.

Male Long-Evans rats were stereotaxically implanted with a bipolar electrode in the central amygdala and with a stainless-steel cannula in the lateral cerebral ventricle. Rats were then kindled once daily until 3 consecutive Stage 5 kindled seizures were elicited. Adenosine analogues were injected into the lateral cerebral ventricle to examine their effects on behavioral seizures and afterdischarge duration following a kindling stimulus. 5'-N-ethylcarboxamidoadenosine (NECA) and (-)-N-(1-methyl-2-phenylethyl)-adenosine(L-phenylisopropyladenosine) (L-PIA) produced dose-related reductions of amygdaloid-kindled seizures with NECA exhibiting slightly more potent anticonvulsant activity than L-PIA. Parenteral injections of caffeine, at a dose which had no effect on seizure parameters, antagonized the anticonvulsant effects of NECA. These results are consistent with the notion that adenosine is a modulator of synaptic activity in the CNS and methylxanthines exert a specific antagonism of central adenosine receptors.

Adenosine↗

Further studies on the inhibition of adenosine uptake into rat brain synaptosomes by adenosine derivatives and methylxanthines.

Various adenosine derivatives, methylxanthines and other compounds were tested for their abilities to inhibit the rapid uptake of adenosine by rat cerebral cortical synaptosomes. Several pharmacologically potent derivatives of adenosine were weak inhibitors of uptake with IC20 values in excess of 10(-5) M. Derivatives in this category were adenosine-5'-N-ethylcarboxamide, adenosine-5'-cyclopropylcarboxamide, N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine, 1-methylisoguanosine, 2-phenylaminoadenosine and 5-iodotubercidin. Several methylxanthines were very weak inhibitors of adenosine uptake. These included pentoxifylline, n-hexyltheophylline, n-butyltheobromine, and isoamyltheobromine. HL 725, a pyrimido-isoquinoline with potent phosphodiesterase inhibitory activity, inhibited adenosine uptake with an IC20 of 2.0 X 10(-6) M. PK 11195, a putative ligand for the peripheral benzodiazepine binding site did not alter uptake at a concentration of 10(-4) M.

Adenosine↗

Evidence for angiotensin II receptors in the urinary bladder of the rabbit.

Dose-response (DR) curves for several angiotensin analogs were examined on isolated rabbit detrusor strips with washout and rest between each addition. The order of potency was [Val5]-angiotensin II greater than [Ile5]-angiotensin II greater than [Ile5]-angiotensin I greater than [Val4]-angiotensin III. Repeated cumulative DR to [Val5]-AII resulted in a gradual increase in potency and intrinsic activity for four DR. However, the maximum force generated occurred at lower agonist concentrations and was less than that of the single methods, suggesting tachyphylaxis. Atropine (1.0 microM) shifted the cumulative DR curve downward, suggesting some cholinergic component possibly involving a presynaptic site of action. The magnitude of field-stimulated atropine-resistant contractions was reduced by both 1.0 and 10 microM saralasin as well as 10 microM naloxone. Tissue binding with 125I-labelled angiotensin II on isolated detrusor smooth muscle membranes indicated specific binding saturation occurred at 14.3 fmol/mg with a KD of 0.72 nM in EDTA-Tris buffered saline. Thus our results show that angiotensin II (AII) receptors can be demonstrated in destrusor muscle by ligand binding experiments on cell membranes and that saralasin and naloxone partially block atropine-resistant contractions. However, it seems unlikely that AII serves as a neurotransmitter because of the delay in onset of action of exogenous AII in isolated bath experiments and the apparent inability of saralasin to totally abolish the atropine-resistant field-stimulated preparation. If AII serves a role in neurotransmission it most probably is as a neuromodulator.

Angiotensin II↗

Central effects of adenosine analogs on locomotor activity in mice and antagonism of caffeine.

Mice implanted with chronic indwelling cannulas were injected in the lateral cerebral ventricle with a series of adenosine analogs and the effects on spontaneous locomotor activity were recorded. All analogs produced dose-related decreases in locomotor activity. The relative order of potency for locomotor depression was: NECA much greater than L-PIA greater than CADO greater than D-PIA. Caffeine at the lowest dose produced a significant decrease in locomotor activity. At higher doses caffeine had no effect on locomotor activity but it did antagonize the depressant effects of NECA, a finding consistent with the notion that the central stimulant action of methylxanthines is due to their antagonism of central adenosine receptors.

2-Chloroadenosine↗

Temporal and pharmacological parameters of puromycin-induced amnesia.

Mice were trained in step-down passive avoidance behavior. Bitemporal injections of puromycin (PM) were given either immediately or delayed until 24 hrs after training. PM produced a marked amnesia in both cases during retention testing 3 days later. The amnesia persisted during a second retention test 6 days after training. Of all the antibiotics, only PM is effective as an amnestic agent when injections are delayed 24 or more hours after training. cycloheximide (CXM) was also injected bitemporally immediately after training. However, CXM produced a weaker amnestic effect even though it produced a much greater inhibition of cerebral protein synthesis, more rapidly, and of longer duration. In an effort to attenuate the amnesia produced by PM, in separate experiments, the mice were injected with combined injections of PM and and CXM (bitemporally): mice were also given combined injections of PM (bitemporally) and amphetamine (subcutaneously). The amnesia produced by immediate injections of PM wa not attenuated by either CXM or amphetamine. However, the amnesia produced by delayed injections of PM was attenuated by both CXM and amphetamine. These results suggest that delayed injections of PM (25 hours after training) block the expression or retrieval of memory. This study also supports the contention that puromycin has two separate effects on memory with different temporal parameters depending on when the drug is injected relative to initial training.

Amnesia↗

Chronic oesophageal fistulation for studying oropharyngeal and gastric influences on ingestive behaviour in the pigeon.

Surgical and postoperative procedures were developed in the pigeon to study the influence of oropharyngeal and postingestional factors in the control of food and water intake. Pigeons were prepared with an oesophageal fistula so that material swallowed emerged from a tube exteriorized at the neck. Nutrient solutions were injected into the lower portion of the oesophagus through a feeding tube inserted in the fistula. A postoperative tube-feeding regimen, using commercially available laboratory chow, was established to maintain the pigeon at its preoperative weight.

Anesthesia↗

Brain protein synthesis and memory: the use of antibiotic probes.

The interest in antibiotics as amnestic agents stemmed from their effects on protein synthesis. Initially they were viewed as an avenue for exploring various hypotheses concerning the role of protein synthesis in memory formation. Three classes of protein synthesis inhibitors have been widely used in memory-disruption experiments: puromycin (Puro), the glutarimides such as cycloheximide (CXM) and acetoxycycloheximide, and, more recently, anisomycin (ANI). Each of these agents has been found effective in producing experimental amnesia within dose ranges that are not significantly toxic to the animal. Although a factor common to each is the ability to block protein synthesis, the biochemical mechanisms for protein synthesis inhibition differ for these drugs in a consequential manner. Each of these agents may have other biochemical effects as well. In fact, it appears that protein synthesis inhibition is not a crucial factor underlying their behavioral effects. For example, data from experiments with CXM and ANI suggest that protein synthesis may not be essential for the storage of longer-term memory in mammals, birds, or insects. Even when retention deficits are produced by protein synthesis inhibition, the effects appear to result from deficits in retrieval or access processes rather than in the storage of memory. Puro, on the other hand, appears to exert its effects on memory in a unique manner. Of all the antibiotics, it alone is effective in producing amnesia when injections are delayed until 24 h after training.

Animals↗

Chronic intracarotid cannulation of pigeons for administration of behaviorally active peptides.

Chronic intracarotid cannulation of the common carotid artery was performed in the pigeon. The catheter system of polyethylene tubing consisted of an indwelling component and an injection component. The indwelling component was exteriorized at the occiput so the bird could not reach the catheter with its beak. Following surgery, the pigeons were housed individually and received food and water ad libitum and no special care was necessary. The catheter was flushed daily with heparin in 0.9% NaCl solution to maintain patency. 30 pigeons were continuously or intermittently infused with bioactive peptides for up to 60 days after cannulation.

Animals↗

Puromycin: two distinct behavioral effects with different temporal parameters in the pigeon.

Pigeons were injected intracerebrally with either puromycin (PM) or control saline solution following training for one 12-min session on a visual discrimination. Injections were made either immediately following training, 1 hr later or 24 hr later. Retention testing 3 days after training showed that PM produced marked amnesia in the first two groups, but had no effect in the 24 hr condition. However, all PM groups were retarded subsequently in the number of days required to reach a 90% discimination criterion. This differentiation of two separate behavioral effects with different temporal gradients suggests that PM may be working through two distinct physiological mechanisms.

Animals↗

Preservation of proteins in mummified tissues.

Protein material was extracted from the dessicated tissues of several Egyptian mummies and a frozen Eskimo. The distribution and degree of preservation of high molecular weight protein was analyzed by gel filtration, protein assays, amino acid analysis, and polyacrylamide gel electrophoresis. The protein has undergone considerable degradation although some high molecular weight protein (C. 130,000 daltons) remains intact. Amino acid analysis of the extracted protein indicates the basic amino acids have undergone a chemical modification and may represent a point of preferential breakdown in the polypeptide chain. Atomic absorption spectrophotometry of tissue cations suggests a correlation between degree of preservation of mummified tissue and levels of sodium salts (natron) in the tissue.

Chemical Phenomena↗