Parallel Shift Of Concentration-response Curve Research Articles

The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms.

Parmotremaperlatum is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatum in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca+2 to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K+ (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K+ (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca+2 channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca+2 channels and muscarinic receptors, while the vasodilator effect might be owing to Ca+2 antagonism. Our results provide the pharmacological evidence that P. perlatum could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of P. perlatum as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of P. perlatum in diarrhea, asthma, and hypertension treatment.

Effects of LP-805, a novel vasorelaxant agent, a potassium channel opener, on rat thoracic aorta

1. 1. In rat thoracic aorta, LP-805 (0.1–10 μM) caused the marked reduction of NE-induced maximum response and relaxed the low K + (<35.9 mM)-induced contraction, in a concentration-dependent manner, but failed to relax the high K + (65.9 mM)-induced contraction. 2. 2. Glibenclamide (0.3–1 μM) caused a parallel shift of concentration-response curve produced by LP-805 for 25.9 mM K +-induced contraction and prevented the LP-805-induced reduction in maximum response evoked by NE in a concentration-dependent manner. 3. 3. Glibenclamide (10 μM) prevented the LP-805 (10 μM)-induced decrease in cytosolic Ca 2+ levels which was increased by 1 μM NE or 25.9 mM K +. 4. 4. LP-805 (10 μM) increased basal 86Rb efflux, which was completely inhibited by 10 μM glibenclamide. 5. 5. These results suggest that LP-805 causes a vasorelaxation as a consequence of the decrease in cytosolic Ca 2+ levels due to the increase in K + efflux via opening ATP-dependent K + channels.

The actions of sodium nitroprusside and diltiazem on calcium-, potassium- and histamine-induced contractile responses in isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle.

The effects of sodium nitroprusside (NaNP) and diltiazem on CaCl2-,KCl- and histamine-induced contractile responses were studied in isolated rabbit basilar artery, aorta, taenia coli and trachea. NaNP reduced CaCl2-induced maximal contractions in basilar artery and aorta, but little affected those in taenia coli and trachea. NaNP reduced histamine-induced maximal contraction markedly in aorta but slightly in basilar artery and taenia coli. The reduction in aorta was reversed by increasing CaCl2 contraction in bathing medium. NaNP inhibited histamine-induced contractions of basilar artery, aorta and taenia coli in Ca-free medium. Diltiazem reduced CaCl2-induced maximal contractions in basilar artery and aorta, whilst it caused a parallel shift of concentration-response curves for CaCl2 to the right in taenia coli and trachea. diltiazem reduced histamine-induced maximal contractions in basilar artery and taenia coli. These reductions were reversed by increasing CaCl2 concentration in bathing medium. Diltiazem strongly inhibited histamine-induced contraction of taenia coli in Ca-free medium. The effects of NaNP and diltiazem on KCl-induced contractions both in normal (Ca; 2.5 mM) and in high Ca (Ca; 12.5 mM) media were also studied. From the results obtained in this study, the actions of NaNP and diltiazem were considered to vary with the type of smooth muscle or the condition eliciting contraction. Their possible mechanisms were discussed in this paper.