Academic Journal
Integrated channel plasticity contributes to alcohol tolerance in neurohypophysial terminals.' Mol Pharmacol. 62
| العنوان: | Integrated channel plasticity contributes to alcohol tolerance in neurohypophysial terminals.' Mol Pharmacol. 62 |
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| المؤلفون: | Thomas K Knott, Alejandro M Dopico, Govindan Dayanithi, José Lemos, Steven N Treistman |
| المساهمون: | The Pennsylvania State University CiteSeerX Archives |
| المصدر: | http://molpharm.aspetjournals.org/content/molpharm/62/1/135.full.pdf. |
| سنة النشر: | 2002 |
| المجموعة: | CiteSeerX |
| الوصف: | Short-term ethanol challenge results in the reduction of peptide hormone release from the rat neurohypophysis. However, rats that have been maintained on an ethanol-containing diet for 3 to 4 weeks exhibit tolerance to this effect. Mechanistic underpinnings of this tolerance were probed by examining four ion channel conductances critical for neurohormone release. The voltage-gated L-type calcium channel and the functionally linked calcium-activated BK channel represent a functional dyad. Although these channels show opposite drug responses in the naive terminal (i.e., the L-type Ca 2ϩ channel is inhibited whereas the BK channel is potentiated), the effect of long-term alcohol exposure is to decrease sensitivity to the short-term administration of drug in both instances. In addition to the shift in sensitivity, current density increased for the L-type Ca 2ϩ current and decreased for the BK current, consistent with a compensatory change. Sensitivity to alcohol was also altered for two other channel types studied. Inhibition of the voltagegated transient Ca 2ϩ current was lessened after long-term treatment. I A, which is not sensitive to the drug at clinically relevant concentrations in terminals from the naive rat, acquires sensitivity after long-term exposure, representing a potentially novel type of tolerance. However, neither the transient Ca 2ϩ current nor I A shows a change in current density, demonstrating the selectivity of this aspect of tolerance. Overall, these results demonstrate that channel plasticity can explain at least a portion of the behavioral tolerance resulting from changes in sensitivity of peptide hormone release. Furthermore, they suggest that an understanding of tolerance requires the examination of dynamically coupled channel populations. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1061.8175; http://molpharm.aspetjournals.org/content/molpharm/62/1/135.full.pdf |
| الاتاحة: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1061.8175 http://molpharm.aspetjournals.org/content/molpharm/62/1/135.full.pdf |
| Rights: | Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: | edsbas.1FBB44C0 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |