ALPHA-ADRENOCEPTOR SUBTYPE & CL CURRENT IN PAROTID ACINI

α-肾上腺素能受体亚型

基本信息

  • 批准号:
    6176643
  • 负责人:
  • 金额:
    $ 4.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-08-01 至 2002-07-31
  • 项目状态:
    已结题

项目摘要

The functional importance of saliva is apparent in patients with xerostomia where lack of saliva results in painful tongue and mucosa; problems with taste and phonation, swallowing, chewing, tooth decay and loss; and increased risk of microbial overgrowth in the oral cavity. Physiologic regulation of salivation results from release of norepinephrine from nerves supplying the parotid gland, which subsequently activates alpha-1 adrenoceptors (alpha1-AR) on parotid acinar cells causing fluid and electrolyte secretion. Alpha1-AR mediated fluid secretion results from the opening of receptor activated Ca2+-dependent Cl- channels. The alpha1-AR subtype causing activation of Ca2+-dependent Cl- channels and fluid secretion is unknown. This study will determine the alpha1-AR subtype that activates Ca2+-dependent Cl- channels in freshly dissociated single cells from rat parotid glands. Alpha1-AR activation of whole-cell Ca2+-dependent Cl- currents will be measured using the perforated-patch configuration of the patch-clamp technique. Alpha1-AR activation of whole-cell Ca2+-dependent Cl- currents in the presence and absence of 5-methylurapidil, WB-4101, and prazosin will be used to determine the alpha1-AR subtype coupled to Cl- efflux and fluid secretion. These drugs are competitive antagonists which are useful in distinguishing the alpha1-AR subtypes known to be present on parotid acinar cells. The effects of oxymetazoline, cirazoline, and xylometazoline in stimulating alpha1-AR induced activation of whole-cell Ca2+-dependent Cl- currents will be measured. These imidazoline agonists will be used to obtain information about the required drug structures needed for varying degrees of receptor-activated Cl- current. Whether or not alpha1-AR modulate Na+-K+ pump activity will be examined using the patch-clamp technique to measure its net outward current. The alpha1-AR subtype modulating Na+-K+ pump activity will also be determined. The present study will add to our understanding of the physiological role of alpha1-AR in regulating fluid secretion in the parotid gland and may provide a rational basis for the design of drugs selective for treating xerostomia.
唾液的功能重要性在口腔干燥症患者中是显而易见的,其中缺乏唾液导致舌头和粘膜疼痛;味觉和发声、吞咽、咀嚼、蛀牙和牙齿脱落的问题;以及口腔中微生物过度生长的风险增加。 唾液分泌的生理调节是由供应腮腺的神经释放去甲肾上腺素引起的,去甲肾上腺素随后激活腮腺腺泡细胞上的α-1肾上腺素受体(α 1-AR),引起液体和电解质分泌。 α 1-AR介导的液体分泌是由受体激活的Ca 2+依赖性Cl-通道的开放引起的。 引起Ca 2+依赖性Cl-通道激活和液体分泌的α 1-AR亚型尚不清楚。 本研究将确定激活大鼠腮腺新鲜分离的单细胞中Ca 2+依赖性Cl-通道的α 1-AR亚型。 将使用膜片钳技术的穿孔膜片配置测量全细胞Ca 2+依赖性Cl-电流的α 1-AR激活。 在存在和不存在5-甲基乌拉地尔、WB-4101和哌唑嗪的情况下,全细胞Ca 2+依赖性Cl-电流的α 1-AR激活将用于确定与Cl-外排和液体分泌偶联的α 1-AR亚型。 这些药物是竞争性拮抗剂,可用于区分已知存在于腮腺腺泡细胞上的α 1-AR亚型。 将测量羟甲唑啉、环唑啉和赛洛唑啉在刺激α 1-AR诱导的全细胞Ca 2+依赖性Cl-电流激活中的作用。 这些咪唑啉激动剂将用于获得不同程度的受体激活的Cl-电流所需的药物结构的信息。 是否α 1-AR调节Na+-K+泵活性将使用膜片钳技术来检测其净外向电流。还将测定α 1-AR亚型调节Na+-K+泵活性。 本研究将增加我们对α 1-AR在调节腮腺液体分泌中的生理作用的理解,并可能为设计选择性治疗口干症的药物提供合理的依据。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Submandibular gland acinar cells express multiple alpha1-adrenoceptor subtypes.
颌下腺腺泡细胞表达多种α1-肾上腺素受体亚型。
Molecular and pharmacological characterization of muscarinic receptor subtypes in a rat parotid gland cell line: comparison with native parotid gland.
大鼠腮腺细胞系毒蕈碱受体亚型的分子和药理学特征:与天然腮腺的比较。
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CHARLES S BOCKMAN其他文献

CHARLES S BOCKMAN的其他文献

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{{ truncateString('CHARLES S BOCKMAN', 18)}}的其他基金

ALPHA-ADRENOCEPTOR SUBTYPE & CL CURRENT IN PAROTID ACINI
α-肾上腺素能受体亚型
  • 批准号:
    2856667
  • 财政年份:
    1999
  • 资助金额:
    $ 4.94万
  • 项目类别:
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