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  • 1990-1994  (1)
  • 1980-1984
  • 1975-1979  (2)
  • 1930-1934
  • glibenclamide  (2)
  • Amino acids  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Blood glucose ; glibenclamide ; immunoreactive insulin ; isopropylnoradrenaline ; mouse ; pancreatic islets ; ultrastructure ; vinblastine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell was studied in mice. Treatment with vinblastine (1.1 μmole/mouse) resulted in a 75% decrease of the amount of normal microtubules and the appearance of characteristic paracrystals. Basal plasma immunoreactive insulin levels were depressed to about 60% of the control level. The dose-response pattern for insulin release (first phase) following two chemically unrelated insulin secretagogues, the potent sulphonylurea derivative, glibenclamide, and the β-adrenergic agonist L-isopropylnoradrenaline, (L-IPNA), was tested with and without vinblastine pretreatment. The dose-response curves for L-IPNA-induced insulin release in vinblastine-treated and control animals did not deviate significantly from each other, whereas insulin release following glibenclamide was almost totally suppressed by vinblastine except at the lowest dose level. Injection of maximal doses of glibenclamide or L-IPNA did not alter the ultrastructural changes induced by vinblastine in the B-cells. It is suggested that the microtubular system of the B-cell might play a minor role for certain insulin-releasing processes and/or that vinblastine might have other important effects on the insulin secretory machinery.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: B-cell ; B-cell granules ; DOPA ; dopamine ; electron microscopic autoradiography ; glibenclamide ; glucose ; insulin secretion ; isopropylnoradrenaline ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation and subcellular localization of dopamine (DA) in pancreatic B-cells and its effects on insulin secretion were investigated in mice following a single injection of L-3,4-dihydroxyphenyl-alanine (L-DOPA). Electron microscopic autoradiography showed that3H-DA formed from administered3H-DOPA was present over B-cells as well as over other types of islet cells. Pretreatment of the animals with a decarboxylase inhibitor greatly reduced the number of autoradiographic grains. In the B-cells the3H-DA-grains were associated with the secretory granules. The location of the label may suggest an incorporation in the periphery of the β-granule, rather than in the dense core, supposed to contain insulin. Accumulation of DA in the B-cells following L-DOPA administration was found to inhibit partially the insulin secretory response to different insulin secretagogues (glucose, glibenclamide and L-isopropylnoradrenaline (L-IPNA)). Treatment with monoamine oxidase inhibitor + L-DOPA induced an almost total suppression of L-IPNA-stimulated insulin secretion, whereas glucose-induced insulin release was still only partially inhibited. Pretreatment with a decarboxylase inhibitor abolished the effects of L-DOPA. It is suggested that intracellularly accumulated DA in the B-cell exerts an inhibitory action on insulin releasing mechanisms induced by different secretagogues and that this action might involve interference with a calcium translocation process at the level of the secretory granule.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1438-2199
    Keywords: Amino acids ; Conditioned avoidance ; Discrimination ; Nerve impulses ; Dopamine ; Excitatory amino acids ; Amphetamine ; Phencyclidine (Rat)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to perform a conditioned avoidance response to white noise in a conventional two-compartment “shuttle-box”. The partition between the compartments had two openings, however, and the correct passage (leftor right) was signalled by changes in background illumination. In this situation the psychotomimetic compoundsd-amphetamine (4 mg kg−1 IP) and phencyclidine (PCP) (2 mg kg−1 SC) were found to selectively disrupt the visual discrimination. Thed-amphetamine-induced abnormal behavior in this situation has previously been linked to excessive dopamine (DA) receptor stimulation, not controlled by nerve impulse flow and its regulation by important local feed-back mechanisms. Thus, the psychotomimetic effects produced by this compound should not only by due to increased DA receptor activationper se, but also to a disruption of normal patterns of firing and release in dopaminergic neurons. There is evidence to suggest that PCP via an excitatory amino acid (EAA) receptor produces a similar net effect on brain meso-limbic dopaminergic neurotransmission via an increased rate of firing, accompanied by regularization of firing (loss of burst activity). In support for a mediation of PCP-induced effects via EAA receptors, the local application of kynurenic acid into the ventral forebrain (4.7µg, bilaterally) was found also to produce a selective disruption of discriminative performance. It should be noted, however, thatd-amphetamine-induced loss of discriminative behavior, but not that induced by PCP, was antagonized by haloperidol (0.1–0.2 mg kg−1 IP) administration. It is thus possible that at least some effects of PCP in this situation are mediated on the efferent side of the dopaminergic neuron. It is suggested that the abnormal behavior, as evidenced by a loss of discriminative (but not avoidance) behavior, is due to disruption of normal, feed-back regulated, nerve impulse flow.
    Type of Medium: Electronic Resource
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