Watts S W, Schenck K W, Cohen M L
Department of Pharmacology and Toxicology, Indiana University, Indianapolis 46227.
Can J Physiol Pharmacol. 1994 May;72(5):463-70. doi: 10.1139/y94-067.
5-Hydroxytryptamine (serotonin, 5-HT) contracts the guinea pig trachea through stimulation of 5-HT2A receptors, an effect previously reported to rapidly desensitize. The present studies were designed to examine further the putative desensitization to serotonin. In vitro studies investigating functional desensitization of the guinea pig tracheal 5-HT2A receptor documented that 5-HT (3 x 10(-7) M) significantly (50%) but incompletely reduced subsequent tracheal maximal contraction to 5-HT. In contrast, an equieffective concentration of carbamylcholine (3 x 10(-8) M) did not reduce guinea pig tracheal contraction to 5-HT. Furthermore, 5-HT (3 x 10(-7) M) did not diminish tracheal contraction to carbamylcholine. These data indicate that 5-HT can selectively desensitize guinea pig tracheal contraction to 5-HT. In addition, 5-HT-induced contraction but not carbamylcholine-induced contraction in guinea pig trachea declined over time, an effect that was more pronounced at high concentrations of 5-HT (1 x 10(-6) and 1 x 10(-5) M). Inhibitors of mechanisms that oppose contractility to 5-HT (5-HT-induced relaxation, uptake of 5-HT, or metabolism of 5-HT) did not reverse the decline in contraction to 5-HT (1 x 10(-5) M). The decline in 5-HT-induced contraction was most rapid in the guinea pig trachea and less so in the rat jugular vein and rat aorta, two preparations in which 5-HT induced contraction also occurred via activation of 5-HT2A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
5-羟色胺（血清素，5-羟色胺）通过刺激5-HT2A受体使豚鼠气管收缩，先前报道该效应会迅速脱敏。本研究旨在进一步研究对血清素的假定脱敏作用。研究豚鼠气管5-HT2A受体功能脱敏的体外研究表明，5-羟色胺（3×10⁻⁷M）显著（50%）但不完全降低随后气管对5-羟色胺的最大收缩反应。相比之下，等效应浓度的卡巴胆碱（3×10⁻⁸M）并未降低豚鼠气管对5-羟色胺的收缩反应。此外，5-羟色胺（3×10⁻⁷M）并未减弱气管对卡巴胆碱的收缩反应。这些数据表明，5-羟色胺可选择性地使豚鼠气管对5-羟色胺的收缩反应脱敏。此外，豚鼠气管中5-羟色胺诱导的收缩而非卡巴胆碱诱导的收缩随时间下降，在高浓度5-羟色胺（1×10⁻⁶和1×10⁻⁵M）时这种效应更明显。对抗5-羟色胺收缩作用的机制抑制剂（5-羟色胺诱导的舒张、5-羟色胺的摄取或5-羟色胺的代谢）并未逆转对5-羟色胺（1×10⁻⁵M）收缩反应的下降。5-羟色胺诱导的收缩反应下降在豚鼠气管中最为迅速，在大鼠颈静脉和大鼠主动脉中则较慢，在这两种制剂中5-羟色胺诱导的收缩反应也通过5-HT2A受体的激活而发生。（摘要截选至250字）
