We demonstrated directly that the TetR repressor utilizes an extrinsic mechanism and CAP, the catabolite activator protein, utilizes an intrinsic mechanism.”
“In
microcoronary endothelial cells (RCEs) from spontaneously hypertensive rats (SHR), the nitric oxide (NO)/cyclic guanosine monophosphate (GMP)-dependent proteinkinase I (cGKI) pathway cannot regulate the cytosolic calcium ([Ca2+](i)) dynamic as in RCEs from Wistar Kyoto rats (WKY). We investigated the altered downstream NO target in SHR cells and, since cGKI expression was low, whether the re-expression of cGKI alpha in SHR RCEs could restore NO calcium responsiveness. We measured Selleck Alvocidib [Ca2+](i) dynamic by fura-2 imaging analysis and the cGKI level by RT-PCR and Western blot in SHR and WKY RCEs. Plasmids encoding for enhanced green fluorescence protein or cGKI alpha-enhanced green fluorescence protein were transiently transfected in SHR RCEs, and [Ca2+](i) was evaluated. Angiotensin-II (AT-II) increased [Ca2+](i)
in a concentration-dependent way in both strains. Whereas in WKY, endogenously produced NO and cyclic GMP analog decreased the AT-II-induced [Ca2+](i); transient, they were ineffective in SHR RCEs. The cGKI level was low in SHR cells. However, after cGKI alpha re-expression, endogenous NO decreased the AT-II-induced [Ca2+](i) transient, while endothelial NO synthase and cGKI inhibition find more prevented it. The low
this website expression of cGKI in SHR accounts for the absent regulation of the agonist-induced [Ca2+](i) transient by the NO/cyclic GMP pathway. Studies on cGKI in humans could contribute to a better understanding of cardiovascular pathologies. Copyright (C) 2012 S. Karger AG, Basel”
“Recent evidence suggests that GABA(A) receptor ligands may regulate ethanol intake via effects at both synaptic and extrasynaptic receptors. For example, the endogenous neurosteroid, allopregnanolone (ALLO) has a similar pharmacological profile as ethanol, and it alters ethanol intake in rodent models. Additionally, recent evidence suggests that delta-subunit-containing extrasynaptic GABA(A) receptors may confer high sensitivity to both ethanol and neurosteroids. The purpose of the present study was to determine the effects of ganaxolone (CAN; an ALLO analog) and gaboxadol (THIP; a GABA(A) receptor agonist with selectivity for the extrasynaptic delta-subunit) on ethanol intake, drinking patterns, and bout characteristics in operant and limited-access self-administration procedures.