Different Types Of Smooth Muscle Research Articles

The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications.

Nigella sativa (N. sativa) is a spice plant which has been traditionally used for culinary and medicinal purposes. Different therapeutic properties including the beneficial effects on asthma and dyspnea, digestive and gynecology disorders have been described for the seeds of N. sativa. There is evidence of the relaxant effects of this plant and some of its constituents on different types of smooth muscle including rabbit aorta, rabbit jejunum and trachea. The relaxant effect of N. sativa could be of therapeutic importance such as bronchodilation in asthma, vasodilation in hypertension and therapeutic effect on digestive or urogenital disorders. Therefore in the present article, the relaxant effects of N. sativa and its constituents on smooth muscles and its possible mechanisms as well as clinical application of this effect were reviewed.

Kcnq Channels in Airway Smooth Muscle

The role of KCNQ (Kv7) channels is well established in neurons, where they play dominant roles in control of resting membrane potentials and cell excitability. Recent studies have revealed expression of KCNQ channels in different types of smooth muscle. Here we focused on airway smooth muscle (ASM), whose membrane potential is primarily, determined by BK-type K+ channels. RT-PCR and immunostaining suggest that KCNQ 1, 4 and 5 are the predominant subtypes in rodent airway. To investigate the contribution of KCNQ channels in cholinergic-induced ASM contraction, we patch-clamped freshly isolated ASM cells and isolated KCNQ current as the non-inactivating component at the end of 2s depolarizations, with BK channels blocked with 1μM paxilline. The KCNQ current was enhanced by the KCNQ channel opener, flupirtine (10μM), and abolished by XE991 (10μM). Although XE991 depolarized the resting membrane potential, it did not affect that of ASM cells pre-treated with carbachol. Similarly, XE991 did not effect carbachol-evoked contractions, whereas flupirtine induced a significant relaxation. The flupirtine effect is likely via opposing voltage-dependent Ca2+ influx, since no effect of flupertine occurred in a low K+ (1mM) bathing solution. Pre-treatment with the muscarinic M3-receptor antagonist, fumarate (5nM), to prevent Gq/11-mediated PIP2 hydrolysis did not reveal an effect of XE991 on contractions, suggesting the mechanism of KCNQ inhibition in ASM is not due to PIP2 depletion. Interestingly, an XE991-dependent increase in contractility was revealed in mice with the β1 BK channel subunit knocked out, an effect enhanced by the M3 receptor antagonist. Thus, KCNQ channels may normally play a secondary role to BK channels in control of cholinergic evoked contractions in ASM; however, given that alteration in BK β1-subunit expression is known to occur in asthma, KCNQ channels in ASM cells may be potential targets for therapeutic intervention in respiratory disease.

Evaluation of the relaxant effect of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in isolated detrusor smooth muscle

The nitric oxide (NO)-independent soluble guanylyl cyclase stimulator stimulator BAY 41-2272 was reported to produce relaxant response in different types of smooth muscle. However no study was carried out to investigate the effects of BAY 412282 in detrusor smooth muscle. Thus, this study aimed to evaluate the relaxant effects of BAY 41-2272, in isolated mouse, rat and rabbit detrusor smooth muscle. Mouse, rat and rabbit were anesthetized, and urinary bladder removed. Detrusor smooth muscle was transferred to 10-mL organ baths containing oxygenated and warmed Krebs-Henseleit solution. Tissues were connected to force-displacement transducers and changes in isometric force were recorded. BAY 41-2272 (0.001-100 microM) produced concentration-dependent detrusor smooth muscle relaxations in mouse, rat and rabbit with maximal responses of 61.3+/-6.6%, 95.1+/-9.9% and 91.7+/-5.9%, respectively. Sodium nitroprusside and glyceryl trinitrate, as well as 8-bromo-cGMP also produced detrusor relaxations, but to a much lesser extent than BAY 41-2272. The NO synthesis inhibitor L-NAME and the phosphodiesterase-5 inhibitor sildenafil had no effect in BAY 41-2272-induced responses. However, the soluble guanylyl cyclase inhibitor ODQ significantly reduced BAY 41-2272-induced relaxations. BAY 41-2272 increased the bladder cGMP levels by about of 14- and 20-fold for 10 and 100 microM, respectively, which were markedly reduced by ODQ. The cAMP levels were unaffected by BAY 41-2272. Moreover, BAY 41-2272 significantly reduced the contractile responses to extracellular Ca(2+) in an ODQ-insensitive manner. In conclusion, rabbit detrusor smooth muscle relaxations by BAY 41-2272 involve mainly cGMP production, but an additional mechanism involving Ca(2+) influx blockade independently of cGMP production appears to be involved.

Characterization of intestinal receptors for VIP and PACAP in rat and in PAC1 receptor knockout mouse.

The receptors for VIP and PACAP were characterized in vitro on rat ileal and colonic longitudinal smooth muscle with adherent myenteric ganglia. Colon strips from PAC1 receptor knockout and wildtype mice were also examined. VIP, PACAP-38 and PACAP-27 all caused concentration dependent relaxations. In rat ileum three different types of smooth muscle VIP/PACAP receptors were defined: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca(2+)-dependent K+ channels, (2) a PAC1 receptor activated by both PACAP-27 and PACAP-38, and (3) a VIP specific receptor regulated by NPY. The receptors identified in rat colon were: (1) a PAC1 receptor localized on NO synthesizing neurones. Activation leads to increased NO production. (2) A smooth muscle PAC1 receptor. The responses elicited by both receptors were abolished by apamin. (3) A smooth muscle VIP specific receptor. PAC1 receptor knockout mice did not respond to PACAP-27 or PACAP-38, whereas VIP induced a relaxatory response indicating the presence of a VIP specific receptor. In wildtype mice all three peptides elicited relaxatory responses. Pharmacological characterization of intestinal VIP/PACAP receptors indicates the existence of receptors, such as a PACAP-27 preferring receptor and a VIP specific receptor, distinct from those that have been cloned (VPAC1, VPAC2, and PAC1).

Pharmacological activities of khellactones, compounds isolated from Peucedanum japonicum THUNB. and Peucedanum praeruptorium DUNN.

The spasmolytic and antiallergic effects of AA and BB, compounds isolated from Peucedanum japonicum THUNB. (P. japonicum THUNB.) and Peucedanum praeruptorium DUNN. (P. praeruptorium DUNN.), were investigated in isolated smooth muscle and rat PCA. AA and BB showed noncompetitive antagonistic effects on Ach- and histamine-induced contraction in the isolated guinea pig ileum. Both AA and BB at 10(-6) g/ml caused a slight shift to the right of the dose-response curve for Ca2+ in isolated guinea pig ileum, and a concentration up to 3 x 10(-6) g/ml displayed noncompetitive antagonistic effects. The Ba2+ (3 x 10(-4) g/ml)-induced contraction in ileum and the histamine (10(-3) g/ml)-induced contraction in trachea were obtained to relaxation by AA and BB in a concentration-dependent fashion. AA and BB showed noncompetitive antagonist action on serotonin-induced contraction of the rat uterus excised 24-48 h after subcutaneous injection of female rats with estradiol. But, AA and BB were found to have hardly any inhibitory effect on rabbit thoracic aorta contractions induced by epinephrine (3 x 10(-6) g/ml). When the effect of oral administration of 40 mg/kg dose of BB was tested on the rat homologous PCA using anti-egg albumin mouse serum dilutions (1:100, 1:250, 1:500 and 1:750), it inhibited the 1:750 serum reaction 42.6%, but the inhibition rates for the other dilutions were 12-20%. Thus, based on the results of testing AA and BB, compounds isolated from P. japonicum THUNB. and P. praeruptorium DUNN. were confirmed to possess a spasmolytic effect on different types of smooth muscle and a mild antiallergic effect. These findings are of interest in regard to the medical uses of P. japonicum THUNB. and P. praeruptorium DUNN. as a herbal drug for bronchial asthma, spasmolytic effect, etc.

Tyrosine Kinase Inhibitors Suppress Agonist-Induced Contraction in Smooth Muscle

Because tyrosine kinases participate in diverse signalling pathways, we suspected that these enzymes might also participate in regulation of signal transduction in smooth muscle. Therefore, we studied the effects of geldanomycin, tyrphostin, and genistein, three structurally unrelated tyrosine kinase inhibitors, on receptor-mediated and depolarization-mediated contraction in three different types of smooth muscle. Contraction elicited by stimulation of muscarinic receptors with carbachol, or by stimulation of alpha-adrenergic receptors with norepinephrine or phenylephrine were markedly (>80%) and reversibly inhibited by tyrosine-kinase inhibitors. In contrast, only slight inhibition (20%) occurred in contractions elicited by K +-induced depolorization. Moreover, tyrphostin did not inhibit direct Ca 2+-mediated activation of the contractile apparatus in preparations permeabilized with β-escin. These results suggest the novel hypothesis that tyrosine kinases participate in regulation of signal transduction that is associated with receptor-mediated contraction of smooth muscle.

ATP inhibits smooth muscle Ca 2+ -activated K + channels

There has been much recent interest in the roles played by smooth-muscle K+ channels in protecting cells against ischemic and anoxic insults and in therapeutic vaso- and bronchodilation (Buckingham 1990; Longmore & Weston 1990). A K+ channel, which is uniquely sensitive to cytoplasmic ATP (KATP), has been identified as a likely candidate for mediating these important functions (Standen et al. 1989). We now show, by using electrophysiological techniques in three different types of smooth muscle, that a large-conductance voltage and Ca2(+)-sensitive channel, otherwise indistinguishable from the the large-conductance Ca2(+)-activated K+ channel (BK channel), is also sensitive to cytoplasmic ATP and cromakalim. ATP, in a dose-dependent manner, decreased the probability of channel opening (Po) of rabbit aortic, rabbit tracheal and pig coronary artery BK channels with a Ki of 0.2-0.6 mM. Cromakalim, 10 microM, partially reversed the ATP induced inhibition and increased Po. Our observations raise the possibility that the ubiquitous BK channel may play a role during pathophysiological events.

Tris(hydroxymethyl)aminomethane inhibits calcium uptake in vascular smooth muscle

This report demonstrates that the commonly used buffering agent Tris(hydroxymethyl)aminomethane (Tris) in concentrations of 5 and 30 mM inhibits calcium (Ca2+) uptake in both rat aortic and portal venous smooth muscle. The data indicates that total exchangeable Ca2+ in portal vein is reduced by about 35% in 5 or 30 mM Tris, while the intracellular exchangeable Ca2+ is not significantly altered. On the other hand, in aortic smooth muscle, while 30 mM Tris reduces total exchangeable Ca2+ by about 20%, intracellular Ca2+ is reduced by 44% in 5 mM Tris and by 55% in 30 mM Tris. The present studies, thus, reveal that Tris exerts significant inhibitory effects on exchangeability and transmembrane movement of Ca2+ in at least two different types of smooth muscle.