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Biomedical subjects

K W Perry

Publications and source records attributed to K W Perry.

At least 73 records · Page 4Linked to original sources
PubMed1982

Depletion of epinephrine in rat hypothalamus by a dopamine agonist, pergolide.

The i.p. injection of pergolide mesylate, a dopamine agonist, at doses of 0.3-0.6 mg/kg led to a decrease in epinephrine concentration in rat hypothalamus. After a 0.6 mg/kg dose of pergolide mesylate, epinephrine concentration in hypothalamus decreased within 2 hr, reached a minimum concentration at about 8 hrs, and then returned toward control values. Norepinephrine N-methyltransferase activity was not decreased after pergolide injection in vivo nor was it inhibited by pergolide added in vitro at concentrations as high as 10(-3) M. Higher i.p. doses of less potent dopamine agonists, apomorphine (10 mg/kg) and lergotrile (3 mg/kg), also decreased epinephrine concentration in hypothalamus. The pergolide-induced decrease in hypothalamic epinephrine concentration was prevented by pretreatment with haloperidol or spiperone, antagonists of dopamine receptors. Activation of dopamine receptors appears to result in a decrease in epinephrine concentration in rat brain, possibly due to enhanced release of epinephrine.

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PubMed1982

Dopamine deficiency in the weaver mutant mouse.

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.

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PubMed1982

Effects of L-dopa on epinephrine concentration in rat brain: possible role of inhibition of norepinephrine N-methyltransferase by S-adenosylhomocysteine.

L-Dopa injected at 200 mg/kg i.p. into rats caused a slight reduction in hypothalamic concentration of epinephrine and completely prevented the accumulation of epinephrine after monoamine oxidase inhibition. The lowering of epinephrine concentration was greater with L-dopa than with D-dopa, was dose-related over a dosage range of 50 to 200 mg/kg of L-dopa and was not prevented by a dopamine receptor antagonist. Hypothalamic norepinephrine N-methyltransferase activity measured in vitro was not altered in rats treated with L-dopa. L-Dopa injection decreased S-adenosylmethionine (SAMe) concentration and increased S-adenosylhomocysteine (SAH) concentration in hypothalamus, probably a result of extensive O-methylation of L-dopa and its metabolites. The decrease in SAMe and epinephrine concentration and the increase in SAH concentration occurred at lower doses of L-dopa in carbidopa-pretreated rats than in control rats. Norepinephrine N-Methyl-transferase activity assayed in vitro was markedly inhibited by SAH; the inhibition was competitive with SAMe as the variable substrate and the Ki for SAH was 1.9 x 10(-5) M. Increasing the SAH/SAMe ratio in in vitro experiments sharply reduced norepinephrine N-methyltransferase activity. The apparent inhibition of hypothalamic epinephrine synthesis in vivo after L-dopa injection is suggested to be a consequence of the increased SAH/SAMe ratio.

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PubMed1981

Ionophore (A23187)-induced efflux of [3H]norepinephrine and endogenous norepinephrine in the rat vas deferens.

The calcium ionophore, A23187, produced a concentration-dependent increase in the release of norepinephrine from nerves in the rat vas deferens. Maximum response to A23187 (10(-6) - 10(-5) M) was delayed in onset, occurring 60-80 min after initiation of continuous superfusion with A23187. In fact. after tissue exposure to A23187 (10(-5) M) for only 5 min with subsequent superfusion in A23187-free buffer, a significant but delayed increase in norepinephrine efflux occurred. The A23187-induced increase in efflux of norepinephrine was not altered when neuronal sodium conductance was blocked with tetrodotoxin (3.1 X 10(-7) M) or when Na+, K+ -stimulated ATPase was blocked with ouabain (10(-4) M). Release of norepinephrine by A23187 was calcium-dependent since A23187-induced efflux of norepinephrine was diminished (approximately 50%), although not abolished, in calcium-free buffer. Thus, one component of A23187 action was calcium independent. A23187 caused an increased efflux of both norepinephrine formed endogenously and [3H]norepinephrine taken up into neuronal stores. However, the effects of A23187, both on rate and maximum amount of release were greater for [3H]norepinephrine than for endogenous norepinephrine. The present studies demonstrate that neurotransmitter efflux can be induced by carboxylic ionophores in a calcium-dependent process, and this approach may prove useful in studies evaluating factors that modulate neurotransmitter release processes.

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PubMed1981

Comparative effects of amantadine and amfonelic acid on dopamine metabolism in rat brain.

Amantadine (50 and 100 mg/kg IP) did not change basal levels of DOPAC (3,4-dihydroxyphenylacetic acid) or HVA (homovanillic acid) in rat brain and did not alter the increase in DOPAC levels resulting from dopamine receptor blockade by spiperone. The increase in HVA levels produced by spiperone was significantly, but only slightly, enhanced by amantadine at these doses. In contrast, amfonelic acid at a dose of 5 mg/kg increased DOPAC and HVA levels and enhanced several-fold the spiperone-induced elevation of DOPAC and HVA levels. Amfonelic acid at at 2.5 mg/kg dose enhanced the turnover of dopamine (measured by the decline in dopamine concentration after inhibition of tyrosine hydroxylation with alpha-methylytyrosine) in spiperone-treated rats, whereas amantadine (100 mg/kg) had a smaller and not statistically significant effect. Neither compound affected significantly dopamine levels in a alpha-methyltyrosine-treated rats not given spiperone. Although amantadine has been observed by earlier workers to enhance the stimulated release of dopamine, it does not appear to act in a manner similar too amfonelic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Sympathetic noradrenergic innervation of guinea-pig liver: histofluorescence and pharmacological studies.

Norepinephrine concentration was higher in guinea-pig liver than in rat or mouse liver and evidence was obtained that the norepinephrine was present within nerves. In guinea pigs, norepinephrine in liver was depleted by reserpine, 6-hydroxydopamine and metaraminol. The depletion by 6-hydroxydopamine and metaraminol was antagonized by prior treatment with desipramine, an inhibitor of uptake into norepinephrine neurons. Guinea-pig liver concentrated metaraminol to a greater extent than did rat liver; the concentration of metaraminol was lowered by desipramine pretreatment and, within three tissues of the guinea pig (heart greater than liver greater than muscle), paralleled the concentration of endogenous norepinephrine. These findings constitute pharmacological evidence for noradrenergic innervation of guinea-pig liver to a greater extent than in other species. Histofluorescence studies confirmed the existence of norepinephrine-containing nerve terminals in guinea-pig liver. Norepinephrine-containing varicosities were seen adjacent to the hepatic artery, portal vein and bile duct in the portal spaces and adjacent to sinusoid capillaries and hepatocytes in the liver parenchyma. These findings strengthen the evidence for sympathetic innervation of liver and suggest the guinea pig as a useful species in exploring physiological roles of noradrenergic innervation of liver.

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