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B D Perry

Publications and source records attributed to B D Perry.

50 records · Page 3Linked to original sources
PubMed1984

Brain epinephrine systems: detailed comparison of adrenergic and noradrenergic metabolism, receptor number and in vitro regulation, in two inbred rat strains.

Epinephrine content and PNMT activity in medulla pons and hypothalamus of F344 inbred rats is from 3- to 8-fold higher than that of Buf inbred rats. These strain-dependent differences in brain adrenergic neurons are reciprocally related to altered alpha 1- adn alpha 2-adrenergic receptor density in PNMT-containing brain regions. Radioligand binding indices related to alpha 2-receptor function reveal that receptors may be 'desensitized' as well as 'down-regulated' in the strain with high PNMT activity (F344), and may be 'supersensitive' as well as 'up-regulated' in the strain with low PNMT activity (Buf). The association between epinephrine-containing neurons and alpha-adrenergic receptor regulation appears specific, since alpha-adrenergic receptor density and regulation in brain regions devoid of PNMT and epinephrine is similar in F344 and Buf rats. While noradrenergic metabolism in F344 rats is greater than that in Buf rats, this difference is generalized throughout the brain and, thus, bears no apparent relationship to the localized alterations in alpha-adrenergic receptor density. Moreover, beta-adrenergic receptor density in the 2 strains is similar in all brain regions. These data suggest that a significant proportion of alpha-adrenergic receptors in medulla-pons and hypothalamus are intimately related to and regulated by epinephrine-containing nerve endings.

Animals↗
PubMed1984

Inheritance of adrenal phenylethanolamine N-methyltransferase activity in the rat.

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-L-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar Km values for the cosubstrate (S-adenosyl-L-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 X Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.

Adrenal Medulla↗
PubMed1984

Assessment of the functional role of brain adrenergic neurons: chronic effects of phenylethanolamine N-methyltransferase inhibitors and alpha adrenergic receptor antagonists on brain norepinephrine metabolism.

The potential role of brain adrenergic neurons in regulating noradrenergic neuronal metabolism was assessed using inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for epinephrine production. Two centrally active PNMT inhibitors (SK&F 64139 and LY134046) were administered over a 6-day treatment period to cause prolonged reductions in epinephrine formation. In brain regions containing endogenous epinephrine (medulla-pons and hypothalamus), chronic treatment with PNMT inhibitors produced: 1) reductions of epinephrine content, 2) elevation of tyrosine hydroxylase activity and 3) elevation of alpha-1 and particularly alpha-2 adrenergic receptor radioligand binding sites; neither norepinephrine turnover nor beta adrenergic receptor binding was affected. In brain regions devoid of endogenous epinephrine (cerebellum, frontal cortex and hippocampus), chronic treatment with PNMT inhibitors produced 1) a variable increase in tyrosine hydroxylase activity (cerebellum only) and 2) a reduction in norepinephrine turnover; neither alpha or beta adrenergic receptor binding was altered. A PNMT inhibitor failing to cross the blood-brain barrier, SK&F 29661, and an alpha-1 adrenoceptor antagonist, prazosin, had no effect on brain catecholamine metabolism. High doses of an alpha-2 adrenoceptor antagonist, yohimbine, increased medulla-pons tyrosine hydroxylase activity but also resulted in prominent reductions in norepinephrine content in all brain regions. The results suggest that prolonged reductions in endogenous brain epinephrine formation produce unique effects on brain norepinephrine function; these effects are regionally distinctive and are qualitatively different from the effects seen with chronic alpha-1 or alpha-2 adrenergic receptor blockade. These data are consistent with regulation of brainstem norepinephrine-containing cell bodies by endogenous adrenergic systems, probably via medullary-pontine alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1983

Interactions of neuroleptic compounds at alpha 2-adrenergic receptor affinity states in bovine caudate nucleus.

Several recent studies have suggested a connection between neuroleptics and/or dopamine systems, and alpha 2-adrenergic receptors. Competition of a variety of neuroleptics at specific alpha 2-adrenergic binding sites (labeled with [3H]rauwolscine or [3H]p-aminoclonidine) in bovine caudate and cortex was examined. Few of the compounds were potent competitors, with (+)-butaclamol, alpha-flupenthixol, clozapine and pimozide the most potent (IC50 range 100-600 nM), while triflupromazine, mesoridazine, and haloperidol were the least potent (IC50 range 5 000-10 000 nM). These findings indicate that few, if any, of the examined neuroleptics have specific, high-affinity interactions with the multiple affinity states of the alpha 2-adrenergic receptor.

Animals↗
PubMed1983

Strain differences in rat brain epinephrine synthesis: regulation of alpha-adrenergic receptor number by epinephrine.

Inbred tht strains Fischer 344 (F344) and Buffalo (BUF) differ in serveral physiological and behavioral measures. It was found that the activity of adrenomedullary and regional brain phenylethanolamine N-methyltransferase is at least four times higher in F344 rats than in BUF rats; these strain-dependent differences corresponded directly with the epinephrine content of the medulla-pons and hypothalamus. Conversely, alpha-adrenergic receptor density in brain regions containing phenylethanolamine N-methyltransferase is two to three times lower in F344 rats than in BUF rats; alpha-receptors in frontal cortex (a brain region lacking phenylethanolamine N-methyltransferase activity and epinephrine) are similar in both strains. These findings suggest that strain-dependent differences in alpha-receptors are regulated by inherited differences in presynaptic adrenergic neuronal function in different brain regions.

Adrenal Medulla↗
PubMed1981

[3H]rauwolscine (alpha-yohimbine): a specific antagonist radioligand for brain alpha 2-adrenergic receptors.

[3H]Rauwolscine, a specific and potent alpha 2-antagonist radioligand, was used to characterize alpha 2-receptor binding in bovine cerebral cortex. [3H]Rauwolscine binding was reversible, stereospecific, and saturable. Association, dissociation, and saturation studies revealed one site interactions (k -1/k+1 = 1.2 nM, KD = 2.5 nM, Bmax = 160 fmol/mg protein) and competition studies indicated that [3H]rauwolscine labeled the alpha 2-receptor. Agonists inhibited [3H]rauwolscine binding in a shallow, GTP-sensitive manner. These results suggest that [3H]rauwolscine specifically labels both the high and low affinity states of the alpha 2-receptor in brain membranes.

Animals↗
PubMedDate not supplied

Ecology and epidemiology of raccoon rabies.

Two areas of the United States presently are experiencing epizootics of raccoon rabies, which have been followed by the development of an enzootic state. These include four southeastern and five mid-Atlantic states. Information was obtained from 1,610 raccoons submitted for rabies testing in four of the affected mid-Atlantic states during 1982 and 1983 and from 798 raccoons from Virginia during 1984 and 1985. Analysis of the two sets of data provided an opportunity to characterize certain aspects of the epizootic. Raccoons collected during the day or at dusk and those that behaved abnormally were more likely to be rabid. Many human exposures to raccoons were preventable or may not have necessitated treatment. Eight (3%) of 291 serum samples from raccoons in an epizootic area had titers of antibody to rabies virus (complete neutralization) of greater than or equal to 1:25. Field trials of baiting systems incorporating an oral raccoon rabies vaccine are being conducted in Virginia, Washington, D.C., and Pennsylvania.

Animals↗
PubMedDate not supplied

Serological study of ovine toxoplasmosis in Colombia: prevalence of haemagglutinating antibodies to toxoplasma in sheep.

A total of 1655 ovine sera from the six principal sheep rearing areas of Colombia were examined for toxoplasma antibodies using the indirect haemagglutination test. It was shown that 58 per cent of these samples had titres of 1/16 or greater. Seropositive animals were distributed throughout all the areas studied. The possible factors affecting the distribution of seropositive sheep in one of the areas are discussed.

Animals↗
PubMedDate not supplied

Prenatal exposure to drugs of abuse in humans: effects on placental neurotransmitter receptors.

Recently, the concept of behavioral teratology has evolved. In animal models, prenatal exposure to low doses of psychotropics (e.g., methadone, diazepam) results in abnormal development of behavior. Furthermore, in animals, pre- and perinatal exposure to psychoactive drugs results in altered brain neurochemistry. In humans, similar behavioral and neurological disruptions have been reported. The mechanisms responsible for these effects are unknown; however, all of these psychotropics have high affinity, specific interactions with various neurotransmitter receptors. Furthermore, normal development of nervous tissue appears to be mediated through neurotransmitter receptors. Disruption of normal, receptor-mediated "signals" by psychoactive agents would be expected to alter development of brain. In order to examine the regulation of neurotransmitter receptors by centrally acting agents, we have compared placental neurotransmitter receptors from "control" and substance-abusing women, hypothesizing that (1) placental neurotransmitter receptor regulation may mirror fetal brain neurotransmitter receptor regulation and (2) placental neurotransmitter receptors themselves may play a role in development. Standard radioligand binding methods were employed. Control values were relatively consistent while substance-abusing values were inconsistent, with wide variation in each substance-abusing group, possibly indicative of "regulation" of neurotransmitter receptors, yet certainly complicated by other variables surrounding gestation and birth (e.g., drug dosage and schedule, length of labor). In this regard, levels of neurotransmitter receptors were consistently higher (20-100%) in caesarian section tissue, possibly reflecting "down-regulation" of neurotransmitter receptors in placentas by the known excess sympathetic and opiate activity during labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗