Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China. Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.

1. The time course of nitric oxide synthase (NOS) activity in neuronal, endothelial, and glial cells in the rat striatum after middle cerebral artery (MCA) occlusion and reperfusion was examined using a histochemical NADPH-diaphorase staining method. 2. In sham-operated rats, neuronal cells of the striatum exhibited strong NADPH-diaphorase activities. When rats were subjected to MCA occlusion for 1 hr, neuronal damage, including neurons with positive NADPH-diaphorase activities, appeared in the striatum at 3 hr after and extended to all areas of the striatum 3-4 days after reperfusion. 3. NADPH-diaphorase activities in the endothelial cells increased in the damaged part of striatum from 3 hr after, peaked at 1-2 days after MCA occlusion/reperfusion, then gradually decreased. 4. In parallel with the development of neuronal damage, some astrocytes and a high proportion of microglia/macrophages located in the perisite and in the center of the damaged striatum, respectively, exhibited a moderate to high level of NADPH-diaphorase activities. Most of these activities disappeared at 4 days after MCA occlusion. 5. These findings provided evidence that an inappropriate activation of NOS in endothelial cells and microglia/macrophages, in response to MCA occlusion/reperfusion, is closely associated with initiation and progression of ischemic neuronal injury in the striatum.

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ABSTRACT-The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific The bladder functions are controlled by the integration of excitatory, inhibitory and sensory nerve activity in the spinal cord, pons and forebrain; and 5-hydroxytryptamine (5-HT) has been identified as an inhibitory neurotransmitter in the micturition reflex pathway at spinal and supraspinal sites (1). In vivo studies have shown that the 5-HT1A receptor of some 5-HT receptor subtypes are important in the micturition reflex pathway (2 -4), especially at the spinal site (4). In vitro study has shown that 5-HT causes contractions of urinary bladder preparations from several mammals (5). In most species, activation of 5-HT 2 receptor has been reported to cause contractions due to direct stimulation of smooth muscle cells of cat (6, 7) and human (8) urinary bladder. Activation of 5-HT 3 receptor causes neurogenic contractions mediated by stimulation of the receptor located on the excitatory neurons in the cat (7), mouse (9), guinea pig (10), rabbit (11, 12), and human (13, 14). The 5-HT4 receptor has been suggested to be located on the excitatory neurons of urinary bladder and its activation facilitates cholinergic transmission in humans (14,15), while in the monkey urinary bladder, the 5-HT4 receptor is located post-junctionally and its activation causes inhibition of neurogenic contractions (16). In the guinea pig urinary bladder, it has been reported by mechanical experiments that 5-HT2A and 5-HT4 receptors are involved in enhancing purinergic transmission and the 5-HT 3 receptor is involved in enhancing cholinergic transmission (10).In order to elucidate the function of 5-HT receptor subtypes, especially 5-HT4 receptor in the urinary bladder, and interaction between localization and function of 5-HT 4 receptor, we examined effects of 5-HT and 5-HT antagonists on the responses to 5-HT using mechanical activity, acetylcholine (ACh) release and in vitro receptor autoradiography.

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