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1.
2.
Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors 总被引:4,自引:0,他引:4
M C Michel J W Regan M A Gerhardt R R Neubig P A Insel H J Motulsky 《Molecular pharmacology》1990,37(1):65-68
We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989)]. We now have used three approaches to distinguish the nonadrenergic [3H]idazoxan sites from alpha 2-adrenergic receptors. (a) No nonadrenergic [3H]idazoxan binding sites were found in COS-7 cells transfected with the genes for the two known alpha 2-adrenergic receptor subtypes. (b) The ratio of alpha 2-adrenergic and nonadrenergic [3H]idazoxan sites in human platelet membranes varied considerably between various donors. (c) Highly purified platelet plasma membranes were enriched for alpha 2-adrenergic receptors but did not contain any nonadrenergic [3H]idazoxan binding sites. We conclude that the nonadrenergic [3H]idazoxan binding sites are not co-expressed with alpha 2-adrenergic receptors and at least in human platelets may be located in an intracellular compartment. 相似文献
3.
Ron Langevin PhD Jerald Bain MD 《Sexual abuse : a journal of research and treatment》1992,5(2):99-118
Thirteen diabetic male sex offenders were compared to 13 nondiabetic sex offenders matched on age, education and offense type. A standard battery of tests administered in the assessment of sex offenders was used to compare the two groups. The tests examine sexual history and preference, substance abuse, violence, personality, and neuropsychological impairment. Results showed that diabetics more often than controls complained of impotence and were nonresponders during phallometric testing. Diabetics, as adults, tended to have less sexual experience with adults and more with pubescent females. The two groups did not differ in number of sexual or nonsexual offenses. The diabetics reported more problems controlling their emotions and more often than controls presented in assessment with inappropriate and/or aggressive behavior and poor cooperation. MMPI results showed diabetics to have more overall clinical disturbance than controls including anxiety, health concerns, family problems, authority problems, criminality, confused thinking and ruminating. Diabetics and controls did not differ in reported frequency of violent behavior but the diabetics responded more extremely, given the circumstances. Diabetics tended to show more violence to their own children. The role of diabetes in the relapse cycle model of offending is discussed. 相似文献
4.
Thomas R. Insel 《Neuropsychopharmacology》2007,62(12):1337-1339
5.
Mark D Herron Sheryll L Vanderhooft Carrie Byington Jerald D King 《Journal of perinatology》2003,23(3):256-259
Aspergillosis is an uncommon neonatal infection, diagnosed with an increasing frequency over the last two decades. We report a premature neonate who developed aspergillosis while receiving amphotericin B and fluconazole for candidiasis. Despite early recognition and diagnosis, the infant died. We review the clinical appearance of Aspergillus species, the distinctions between primary cutaneous aspergillosis and invasive aspergillosis, and advances in diagnosis and treatment. 相似文献
6.
James T. Winslow Thomas R. Insel 《Progress in neuro-psychopharmacology & biological psychiatry》1991,15(6):745-757
1. Rat pups emit ultrasonic calls during brief episodes of social separation. These calls have been variously described as “distress” calls and may be related to the separation cries expressed by the young of many mammalian species.
2. Ultrasonic call of rat pups are modulated by environmental stimuli such as ambient temperature, olfactory and tactile stimuli associated with the nest.
3. Calls are also sensitive to a variety of purported anxiolytic and anxiogenic drugs, including the benzodiazepines, serotonin agonists, and ligands at the NMDA-glycine receptor complex.
4. In addition to providing a simple test for the anxiolytic properties of drugs, this model may also provide new insights about the development and neurobiology of anxiety. 相似文献
7.
We have used two different cultured cell lines--S49 lymphoma cells and BC3H-1 muscle cells--to examine the regulation of beta-adrenergic receptors by receptor antagonists. Rather than an increase ("up-regulation") of receptor number that such antagonists often produce, we found that certain beta-blockers elicit a decrease ("down-regulation") of beta-adrenergic receptors. Alprenolol and propranolol, but not sotalol or ICI 118,551, at concentrations of 10-100 nM down-regulated beta-adrenergic receptors 20-70% following 16-20 hours of treatment of S49 or BC3H-1 cells. Several observations suggest that this phenomenon depends upon beta-receptor interaction, including stereoselectivity [(-)-enantiomers more potent than (+)-enantiomers], blockade of the effect by ICI 118,551, absence of down-regulation of alpha-adrenergic receptors in BC3H-1 cells, and lack of a decrease in beta-adrenergic receptor-independent (forskolin-stimulated) cyclic AMP accumulation in S49 cells. The possibility of retained antagonist interfering with receptor measurement was precluded by the fact that the antagonist-induced decrease in receptor number required several hours incubation and occurred without a prominent change in receptor affinity. The ability of the beta-blockers to elicit down-regulation did not correlate with hydrophobicity of the drugs. Antagonist-induced down regulation of beta-adrenergic receptors did not occur in S49 lymphoma cells that lack the alpha-subunit of Gs, the guanine nucleotide-binding regulatory protein, thus implying a requirement for receptor-alpha s interaction in eliciting beta-receptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
alpha 2-Adrenergic receptors are present on human erythroleukemia (HEL) cells, both on the cell surface and in a sequestered compartment. In the current study we show that benextramine, a hydrophilic irreversible antagonist, can be used to investigate alpha 2-adrenergic receptor compartmentation in these cells. In membranes prepared from HEL cells, benextramine competed for all alpha 2-adrenergic receptors ( [3H]yohimbine sites). In intact cells, at 4 degrees, benextramine exhibited a biphasic competition curve for alpha 2-adrenergic receptors, with EC50 values of approximately 10 microM and greater than 1 mM for the high and low affinity components, respectively. We propose that the alpha 2-adrenergic receptors preferentially blocked by benextramine are those on the surface of the cell, whereas those with low affinity are sequestered receptors because: 1) only epinephrine-accessible sites [i.e., cell surface sites; McKernan et al., Mol. Pharmacol. 32:258-265 (1987)] are removed by prior treatment of cells with benextramine, 2) a preparation enriched with surface membranes is also enriched in receptors with a high affinity for benextramine; and 3) after blockade of cell surface receptors (54 +/- 6% of total sites, n = 7) by benextramine, the ability of the alpha 2-adrenergic agonists epinephrine and UK-14,304 to inhibit forskolin-stimulated cAMP accumulation is lost. The latter result implies that only cell surface and not sequestered receptors are functionally coupled to adenylate cyclase. The return of receptors from the sequestered compartment to the cell surface and the recovery of alpha 2-adrenergic receptor function were measured after HEL cells were treated with benextramine (50 microM for 1 hr at 4 degrees). The recovery of receptor binding (t1/2 = 25 min) was somewhat slower than the recovery of function (t1/2 approximately 8 min). This is consistent with the existence of "spare receptors" and also suggests that the sequestered compartment of alpha 2-adrenergic receptors can rapidly exchange with those on the surface. When all alpha 2-adrenergic receptors were blocked by incubation of HEL cells with benextramine for 1 hr at 37 degrees, repopulation of surface and sequestered receptors was much slower (t1/2 = 9 hr for recovery of total receptors). Surface receptors recovered even more slowly than did total cellular receptors consistent with the idea that alpha 2-adrenergic receptors must traverse through intracellular locations before insertion into the cell surface.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
9.
Robert A. Kinsman Enrique Fernandez Marsha Schocket Jerald F. Dirks Nicholas A. Covino 《Journal of behavioral medicine》1983,6(4):339-357
Subjective symptoms and experiences were explored within a group of 146 severe, chronic bronchitis and emphysema patients. Eighty-nine symptoms and experiences, derived from initial interviews with 29 patients, were rated according to the frequency of occurrence during breathing difficulties. Key cluster analyses were used to derive a Bronchitis-Emphysema Symptom Checklist (BESC) measuring 11 symptom categories: Helplessness-Hopelessness, Decathexis, Fatigue, Poor Memory, Peripheral-Sensory Complaints, Dyspnea, Congestion, Sleep Difficulties, Irritability, Anxiety, and Alienation. The BESC symptom categories are highly reliable and the relationships among categories are stable across two subgroups of patients. The BESC provides one way to describe how patients cope with and experience chronic bronchitis and emphysema. 相似文献
10.