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  • 1
    ISSN: 1573-6903
    Keywords: Dopamine receptors ; quinpirole hypothermia ; D2 receptors ; D1/D2 receptor interaction ; temperature regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of centrally and peripherally administered dopamine D1 and D2 specific compounds on core body temperature in mice was investigated. Quinpirole (LY-17155), a D2 agonist, induced a dose-dependent fall in body temperature (2.4–11.6%; p〈0.003) when injected intraperitoneally (ip, 0.3–3.0 mg/kg) and intracerebroventricularly (icv, 0.1 mg/kg). This quinpirole-induced (1.0 mg/kg, ip) hypothermia was reversed by the central and peripheral administration of the D2 antagonists S-(−)-sulpiride (3.0–30.0 mg/kg, ip; 0.1–3.0 mg/kg, icv) and spiperone (0.03 and 0.1 mg/kg, ip; 0.03–3.0 mg/kg, icv). Domperidone, a D2 antagonist which does not cross the blood brain barrier, had no effect on quinpirole-induced hypothermia (1.0–10.0 mg/kg, ip). Domperidone partially reversed quinpirole-induced hypothermia at 0.1–30.0 mg/kg, icv. The D1 agonist, SKF-38393 at a high dose of 10.0 mg/kg, ip mildly attenuated quinpirole-induced hypothermia (a 1.8% increase in temperature). SKF-38393 at 10.0 mg/kg, icv potentiated quinpirole-induced hypothermia. SCH-23390 (0.1–3.0 mg/kg, ip), a D1 antagonist, had no effect on quinpirole-induced hypothermia and potentiated the hypothermia when administered icv. An ineffective icv dose of spiperone (0.01 mg/kg) in reversing quinpirole-induced hypothermia was rendered effective by prior administration of SCH-23390 (0.1–3.0 mg/kg, icv) but not by SKF-38393 (1.0–10.0 mg/kg, icv). These data suggest a central D2 receptor mechanism mediating hypothermia in mice which is capable of being modulated by the D1 receptor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6903
    Keywords: NMDA ; [3H]MK-801 ; dog brain ; spinal cord ; rodent brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The biochemical and pharmacological properties of [3H]MK-801 binding to the N-methyl-d-aspartate (NMDA) receptor-channel in homogenates of mouse, guinea pig and dog brain, dog cerebral cortex and rat spinal cord were determined using radioligand binding techniques. Specific [3H]MK-801 binding increased linearily with increasing tissue concentration and in general represented 80–93% of the total binding at 6–8 nM radioligand concentration. [3H]MK-801 interacted with brain and spinal homogenates with high affinity. The dissociation constants (K d ) for all tissues studied were similar ranging between 7.9 and 11.9 nM, whereas the maximum number of binding sites (Bmax) showed a wide, tissue-dependent range (0.1–6.75 pmol/mg protein). The rank order of tissue enrichment was found to be as follows: mouse brain〉〉dog cerebral cortex〉〉dog brain〉〉 guinea pig brain〉〉rat spinal cord. Specific [3H]MK-801 binding in rodent and dog brain, dog cerebral cortex and rat spinal cord exhibited a similar pharmacological profile 9correlation coefficients=0.93–0.99). The rank order of potency of unlabelled compounds competing for [3H]MK-801 binding was: (+)MK-801〉(−)MK-801〉phencyclidine〉(−)cyclazocine〉〉(+)cyclazocine ≥ ketamine〉(+)N-allyl-N-normetazocine〉(−)N-allyl-N-normetazocine〉(−)pentazocine〉(+)pentazocine. NMDA, Kainate, quisqualate and several other compounds failed to inhibit [3H]MK-801 binding at 100 μM. In modulation studies conducted on extensively washed dog cortex membranes, Mg2+ ions stimulated [3H]MK-801 binding at 10 μM-1 mM (EC50=91.5 μM) and then inhibited the binding from 1 mM to 10 mM (IC50=3.1 mM). Glycine stimulated [3H]MK-801 binding at 30 nM-1 mM (EC50=256 nM). In contrast, Zn2+ ions inhibited the binding of [3H]MK-801 binding site exhibited similar pharmacological and biochemical properties. These data appear to suggest that the pharmacological profile of the NMDA-receptor-channel is species and tissue independent.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6903
    Keywords: Dopamine receptors ; autoradiography ; hypertension ; schizophrenia ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of chronic dietary sodium chloride (NaCl) consumption on renal function and brain dopamine receptors were studied in adult, male normotensive rats. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited significant increases in plasma aldosterone, chloride and changes in urinary electrolyte excretion. In contrast, rats maintained on the high NaCl (8%) diet for 4 weeks demonstrated significant increases in urine volume and urinary sodium, chloride and dopamine excretions and water intake. Rats fed the high NaCl diet displayed a 42–59% decrease (p〈0.001–0.05) in D1 binding in the nucleus accumbens (NA), olfactory tubercle (OT) and the striatum (STM), without any effects on D2 binding in these brain regions. Rats maintained on the low NaCl diet also demonstrated decreased D1 binding in the ventral (24%, p〈0.02) and lateral (29%, p〈0.01) STM, but not in the OT, NA, entopeduncular nucleus and substantia nigra. Rats fed low or high NaCl diets exhibited a 35–180% increase (p〈0.01–0.05) in D2 binding in several mid-brain areas (e.g. hypothalamus, thalamus and hippocampus) and hindbrain regions (e.g. superior colliculus and nucleus tractus solitarius) without affecting the D1 binding. These data indicate that chronic modification of dietary salt intake profoundly affects the renal handling of sodium/water excretion and leads to selective up- and/or down-regulation of DA receptor subtypes in different areas of the brain. These findings may have relevance to centrally-mediated hypertension, Parkinson's disease, schizophrenia and other brain disorders involving dopamine and dopamine receptors.
    Type of Medium: Electronic Resource
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