Enhancement of 5-HT2A receptor function and blockade of Kv1.5 by MK801 and ketamine: implications for PCP derivative-induced disease models.

MK801 and ketamine, which are phencyclidine (PCP) derivative N-methyl-d-aspartate receptor (NMDAr) blockers, reportedly enhance the function of 5-hydroxytryptamine (HT)-2A receptors (5-HT2ARs). Both are believed to directly affect the pathogenesis of schizophrenia, as well as hypertension. 5-HT2AR signaling involves the inhibition of Kv conductance. This study investigated the interaction of these drugs with Kv1.5, which plays important roles in 5-HT2AR signaling and in regulating the excitability of the cardiovascular and nervous system, and the potential role of this interaction in the enhancement of the 5-HT2AR-mediated response. Using isometric organ bath experiments with arterial rings and conventional whole-cell patch-clamp recording of Chinese hamster ovary (CHO) cells ectopically overexpressing Kv1.5, we examined the effect of ketamine and MK801 on 5-HT2AR-mediated vasocontraction and Kv1.5 channels. Both ketamine and MK801 potentiated 5-HT2AR-mediated vasocontraction. This potentiation of 5-HT2AR function occurred in a membrane potential-dependent manner, indicating the involvement of ion channel(s). Both ketamine and MK801 rapidly and directly inhibited Kv1.5 channels from the extracellular side independently of NMDArs. The potencies of MK801 in facilitating the 5-HT2AR-mediated response and blocking Kv1.5 were higher than those of ketamine. Our data demonstrated the direct inhibition of Kv1.5 channels by MK801/ketamine and indicated that this inhibition may potentiate the functions of 5-HT2ARs. We suggest that 5-HT2AR-Kv1.5 may serve as a receptor-effector module in response to 5-HT and is a promising target in the pathogenesis of MK801-/ketamine-induced disease states such as hypertension and schizophrenia.

Understanding women, health, and social change: the case of South Korea.

Since the 1960s, South Korea has experienced rapid economic development and an improvement in the health of its population. During this period there have been marked increases in women's educational and occupational opportunities. But despite these improvements, women still suffer higher levels of gender discrimination than their counterparts in many other countries at similar stages of development. Most dramatically, there are still high levels of sex-selective abortion. Women have lower socioeconomic status than men, and their lives are markedly restricted by the cultural values associated with Confucianism. This article explores the effects of these factors on women's health. Despite their greater longevity, South Korean women still report higher rates of morbidity and distress than men. This can be compared with the "gender paradox" in health reported in many developed countries during the 1970s and 1980s. More detailed research is needed on the factors influencing the health of South Korean women and on related trends in other newly industrializing Asian societies.