Publications (2)2.84 Total impact
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ABSTRACT: CCK is a brain-gut peptide that is abundantly distributed in both gastrointestinal tract and mammalian brain. The sulfated octapeptide fragment of cholecystokinin (CCK-8S) has been shown to be involved in numerous physiological functions such as behavior, anxiety, learning/memory processes and neuropathic pain. CCK-8S is one of the strongest endogenous anti-opioid substances and suppresses opioid peptides-mediated 'pre-synaptic inhibition' of gamma-aminobutyric acid (GABA) release. Here we provide evidence that CCK-8S modulates GABA-evoked membrane depolarization in rat dorsal root ganglion (DRG) neurons using intracellular recording technique. Bath application CCK-8S-induced membrane depolarization in most of the rat DRG neurons. The depolarization was blocked by prolumide but not LY225910. Pretreatment with CCK-8S suppressed the GABA-evoked depolarization in a concentration-dependent manner. The CCK-8S inhibition was also time-dependent and reached the peak at about 2 min. The inhibitory effect of CCK-8S was strongly suppressed by pre-incubation of CCK-B receptor antagonist LY225910, phospholipase C inhibitor U73122, protein kinase C inhibitor chelerythrine and calcium chelator BAPTA-AM, respectively. The protein kinase A inhibitor H-89 did not affect CCK-8S effect. The results suggest that CCK-8S inhibits GABA-A receptor function by activation of CCK-B receptor followed by activation of intracellular PLC-Ca(2+)-PKC cascade. Thus, CCK-8S might enhance nociceptive information transmission through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in modulation of primary sensory information (especially pain).
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ABSTRACT: Chloride channels have been identified in vascular smooth muscle cells (SMCs). It has been shown that these channels are involved in myogenic tone regulation and neuromuscular transmission in various vascular beds. However, whether the chloride channels are responsible for the formation of excitatory junction potentials (EJPs) of SMCs in the spiral modiolar artery (SMA) remains unelucidated. In the present study, the effects of chloride channel blockers (niflumic acid, NFA; indanyloxyacetic acid 94, IAA-94; disodium 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonate, DIDS) on EJP were explored in guinea pigs, using intracellular recording techniques on acutely isolated SMA. It was found that EJP was evoked in the majority of the SMCs (75%, n=49) with an adequate electronic stimulation. The amplitude of the EJP was partially blocked (30% approximately 80%) by combined application of alpha(1) receptor antagonist (prazosin) and alpha(2) receptor antagonist (idazoxan) at concentration of up to 1 micromol/L, and P(2x) receptor antagonist (PPADS, 10 approximately 100 micromol/L). NFA (100 micromol/L) could further inhibit the residual EJP in the presence of alpha(1), alpha(2)-adrenergic and P(2x) receptor antagonists. IAA-94 or DIDS not only inhibited the amplitude but also shortened the duration of EJP. Decrease of extracellular chloride concentration from 135.6 mmol/L to 60 mmol/L would enhance EJP. Moreover, IAA-94 (100 micromol/L) and DIDS (200 mumol/L) could reverse the enhancement of EJP by low extracellular Cl(-). NFA (100 micromol/L) could also block the residual depolarizations evoked by norepinephrine (NE, 1 approximately 50 micromol/L). Based on these results, it is inferred that NE could activate a novel adrenoceptor to open the chloride channel on the membrane of the SMCs, leading to a transmembrane Cl(-) current. This current is involved, at least partially, in the formation of EJP.
shihezi universityShikhedzy, Xinjiang Uygur Zizhiqu, China