PubMed · 15487075
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Sindhu R Johnson, Catharine Dewar. 2004. Erectile dysfunction and scleroderma.. https://pubmed.ncbi.nlm.nih.gov/15487075/
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Based on the results of independent studies the involvement of norepinephrine in REM sleep regulation was known. Isolated studies showed that the effect could be mediated through either one or more subtypes of adrenoceptors. Earlier we have reported that REM-OFF neurons continue firing during REM sleep deprivation and mild but continuous stimulation of locus coeruleus (LC) or picrotoxin injection into the LC, that did not allow the REM-OFF neurons in the LC to stop firing, reduced REM sleep. However, the mechanism of action and type of adrenoreceptors involved in REM sleep regulation were unknown. The possible mechanism of action has been investigated in this study. It was proposed that if LC stimulation-induced decrease in REM sleep was due to norepinephrine, adrenergic antagonist must prevent the effect. Therefore, in this study, the effects of alpha1, alpha2 and beta-antagonists, viz. prazosin, yohimbine and propranolol, respectively, and alpha2 agonist, clonidine, on LC stimulation-induced reduction in REM sleep were investigated. The results showed that stimulation of LC inhibited REM sleep by reducing the frequency of generation of REM sleep, although the duration per episode remained unaffected. This decrease in the frequency of REM sleep was blocked by beta-antagonist propranolol while the duration of REM sleep per episode was blocked by alpha1-antagonist, prazosin. Also, a critical level of norepinephrine in the system was required for the generation of REM sleep, however, a higher level may be inhibitory. Based on the results of this study and our earlier studies, an interaction between neurons, containing different neurotransmitters and their subtypes of receptors for LC-mediated regulation of REM sleep has been proposed.
BACKGROUND: We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). METHODS: Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty-seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)-alpha-related activity were identified. CONCLUSIONS: Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell-cell signaling/signal transduction, and transcriptional regulation.
AIM: To investigate the effect of rhubarb on contractile response of isolated gallbladder muscle strips from guinea pigs and its mechanism. METHODS: Guinea pigs were killed to remove the whole gallbladder. Two or three smooth muscle strips (8 mm x 3 mm) were cut along the longitudinal direction. The mucosa on each strip was carefully removed. Each longitudinal muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees), bubbled continuously with 950 mL/L O(2) and 50 mL/L CO(2). The resting tension (g), mean contractile amplitude (mm), and contractile frequency (waves/min) were simultaneously recorded on recorders. After 2-h equilibration, rhubarb (10, 20, 70, 200, 700, 1,000 g/L) was added cumulatively to the tissue chamber in turns every 2 min to observe their effects on gallbladder. Antagonists were given 3 min before administration of rhubarb to investigate the possible mechanism. RESULTS: Rhubarb increased the resting tension (from 0 to 0.40+/-0.02, P<0.001), and decreased the mean contractile amplitude (from 5.22+/-0.71 to 2.73+/-0.41, P<0.001). It also increased the contractile frequency of the gallbladder muscle strips in guinea pigs (from 4.09+/-0.46 to 6.08+/-0.35, P<0.001). The stimulation of rhubarb on the resting tension decreased from 3.98+/-0.22 to 1.58+/-0.12 by atropine (P<0.001), from 3.98+/-0.22 to 2.09+/-0.19 by verapamil (P<0.001) and from 3.98+/-0.22 to 2.67+/-0.43 by phentolamine (P<0.005). But the effect was not inhibited by hexamethonium (P>0.05). In addition, the action of mean amplitude and frequency was not inhibited by the above antagonists. CONCLUSION: Rhubarb can stimulate the motility of isolated gallbladder muscle strips from guinea pigs. The stimulation of rhubarb might be relevant with M receptor, Ca(2+) channel and alpha receptor partly.