Background: The contribution of histamine (H1) receptors inhibitory and/or β-adrenoceptors stimulatory mechanisms in the relaxant property of Ferula assa-foetida. (F. asafoetida) was examined in the present study. Methods: We evaluated the effect of three concentrations of F. asafoetida extract (2.5, 5, and 10 mg/mL), a muscarinic receptors antagonist, and saline on methacholine concentration-response curve in tracheal smooth muscles incubated with β-adrenergic and histamine (H1) (group 1), and only β-adrenergic (group 2) receptors antagonists. Results: EC50 values in the presence of atropine, extract (5 and 10 mg/mL) and maximum responses to methacholine due to the 10 mg/mL extract in both groups and 5 mg/mL extract in group 1 were higher than saline (P < 0.0001, P = 0.0477, and P = 0.0008 in group 1 and P < 0.0001, P = 0.0438, and P = 0.0107 in group 2 for atropine, 5 and 10 mg/mL extract, respectively). Values of concentration ratio minus one (CR-1), in the presence of extracts were lower than atropine in both groups (P = 0.0339 for high extract concentration in group 1 and P < 0.0001 for other extract concentrations in both groups). Conclusion: Histamine (H1) receptor blockade affects muscarinic receptors inhibitory property of F. asafoetida in tracheal smooth muscle
Receptors, Muscarinic

No abstract available.
Autoradiography* ; Brain* ; Rats, Wistar* ; Receptors, Muscarinic*

Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. A TRPC4 specific activator, (–)-englerin A, induced both current and calcium fluorescence with the similar time course. Muscarinic receptor stimulator, carbachol, also induced both current and calcium fluorescence with the similar time course. By forming heteromers with TRPC4, TRPC1 significantly reduced the inward current with outward rectifying I-V curve, which also caused the decrease of calcium fluorescence intensity. These results suggest that GCaMP6s attached to TRPC4 can detect slight calcium changes near TRPC4 channels. Consequently, TRPC4-GCaMP6s can be a useful tool for testing the calcium permeability of TRPC4 channels.
Calcium* ; Carbachol ; Fluorescence ; Permeability* ; Receptors, Muscarinic

BACKGROUND: The stomach can be generally classified anatomically into three parts; fundus, corpus, and antrum. It has not been well demonstrated how the three regions contribute to specified gastric motility. In the present study, the regional differences on contractile response and intracellular Ca2+ levels ([Ca2+]i) were investigated in a mouse gastric muscle. METHODS: An isometrical contraction was measured with a computerized physiograph, and [Ca2+]i was measured with fura-PE3/AM, a fluorescent Ca2+ indicator in gastric smooth muscle from mice. RESULTS: Carbachol (CCh), a potent muscarinic receptor agonist, generated rhythmic contractions in a dose dependent manner, superimposed on tonic components in the antral muscle. Whereas similar contractile responses to CCh was obtained in the antrum, CCh evoked tonic components predominantly. CCh increased [Ca2+]i in a dose dependent manner in both the antral and fundic smooth muscle. However, the increment of [Ca2+]i in the fundus was greater than that of the antrum. Verapamil (10nM), a l-type Ca2+ channel blocker, inhibited completely the contraction and [Ca2+]i induced by CCh in the antral strips, whereas the responses in the fundus showed a resistance to verapamil. CONCLUSIONS: These results suggest that muscarinic stimulation has a regional difference on muscle contractility and [Ca2+]i, which is mediated by differences of Ca2+ movement in mouse gastric muscle.
Animals ; Carbachol ; Mice ; Muscle, Smooth* ; Receptors, Muscarinic ; Stomach ; Verapamil

Overactive bladder(OAB) is a symptom syndrome including urinary urgency with or without urinary incontinence, usually with frequency and nocturia. Urgency, defined as the compelling feeling of impending incontinence that is difficult to defer, is the cornerstone symptom of OAB. The diagnosis is based on symptoms alone and assumes no underlying pathology. Approximately 12.2% of the adult population experience OAB in Korea. The syndrome is now recognized as a chronic debilitating condition that negatively affects the quality of life. Often the patients have a restricted social life and an increased risk for depression. Despite increased awareness in recent years, OAB remains an underreported condition. Continued evolution of our understanding of the pathophysiology of OAB has identified contributory mechanisms, which has in turn established structured evidence-based managements. Treatment of OAB is aimed at relief of symptoms and improving quality of life. Conservative treatments combined with antimuscarinic drugs are the main treatment for OAB. There are many antimuscarinics available, with several under development, which have different specificities for the muscarinic receptors. Other drugs have also been tried but with limited success. Behavioral therapy combined with pharmacological therapy often will bring about acceptable outcomes for patients with OAB. Modalities such as botulinum toxin injections, neuromodulation, and various surgical interventions also are showing encouraging results in more refractory patients. Further research into the basic science of the condition is required to identify the true cause of OAB, allowing new targeted treatments to be established.
Adult ; Botulinum Toxins ; Depression ; Diagnosis ; Humans ; Korea ; Muscarinic Antagonists ; Nocturia ; Pathology ; Quality of Life ; Receptors, Muscarinic ; Urinary Bladder, Overactive* ; Urinary Incontinence

It was attempted to clarify the participation of K+ channels in the post-receptor mechanisms of the muscarinic and A1-adenosine receptor-mediated control of acetylcholine (ACh) release in the present study. Slices from the rat hippocampus were equilibrated with (3H)choline and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Oxotremorine (Oxo, 0.1~10 micrometer), a muscarinic agonist, and N6-cyclopentyladenosine (CPA, 1~30 micrometer), a specific A1-adenosine agonist, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. 4-aminopyridine (4AP), a specific A-type K+-channel blocker (1~100 micrometer), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and 100 micrometer. Tetraethylammonium (TEA), a non-specific K+-channel blocker (0.1~10 mM), increased the evoked ACh release in a dose-dependent manner without affecting the basal release. The effects of Oxo and CPA were not affected by 3 micrometer 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP (10 micrometer- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca2+-free medium, but these were recovered in low Ca2+ medium. And the effects of K+-channel blockers in low Ca2+ medium were inhibited by Mg2+ (4 mM) and abolished by 0.3 micrometer tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca2+ influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and A1-adenosine receptors of the rat hippocampus.
4-Aminopyridine ; Acetylcholine* ; Animals ; Electric Stimulation ; Hippocampus* ; Muscarinic Agonists ; Oxotremorine ; Permeability ; Potassium Channels ; Rats* ; Receptors, Muscarinic ; Tea ; Tetraethylammonium ; Tetrodotoxin

Stimulation of muscarinic receptors by carbachol (CCh) in the circular smooth muscle of the guinea pig gastric antrum causes muscle contraction. In the present study, muscarinic receptor subtype controlling the muscle contraction in response to CCh was studied using putative muscarinic receptor antagonists. Isometric force of the isolated circular muscle strips was measured in an organ bath. CCh contracted the muscle in a dose-dependent way, and each of the three muscarinic receptor antagonists, 4-diphenylacetoxy-N-methylpeperdine methiodide (4-DAMP), methoctramine and pirenzepine shifted the concentration-response curves to the right without significantly reducing the maximum force. The affinities of the muscarinic antagonists (pA2 values) obtained from Schild plot analysis were 10.15, 7.05 and 6.84 for 4-DAMP, methoctramine and pirenzepine, respectively. These results suggest that the M3-subtype mainly mediate the muscle contraction in response to CCh in guinea pig gastric antrum.
Animals ; Baths ; Carbachol ; Guinea Pigs* ; Guinea* ; Muscarinic Antagonists ; Muscle Contraction* ; Muscle, Smooth ; Pirenzepine ; Pyloric Antrum* ; Receptors, Muscarinic*

This study aimed to investigate the mechanism of action of baclofen on the detrusor muscle isolated from rat. Rats (Sprague-Dawley) were sacrificed by decapitation and exsanguination. Horizontal muscle strips of 2 mm x 15mm were prepared for isometric myography in isolated muscle chamber bubbled with 95% / 5%-OZ / CO2 at 371C, and the pH was maintained at 7.4 Detrusor strips. contracted responding to the.. electrical field stimulation (EFS) by 2 Hz, 2U msec, monophasic square wave of 60 VDC. The initial peak of EFS-Induced contraction was tended to be suppresed by a,p-methylene-adenosine 5'-triphosphate (mATP), a partial agonist of purinergic receptor, and baclofen, a GABAB receptor agonist (statistically nonsignificant). The late sustained contraction by EFS was suppressed significantly (p < 0.05) by additions of atropione, a cholinergic muscarinic receptor antagonist and baclofen. The adenosine 5'-triphosphate-induced contraction was completely abolished by mA TP but not by baclofen. In the presence of atropine, the subsequent addition of acetylcholine could not contract the muscle strips: but the addition of acetylcholine in the presence of baclofen evoked a contraction to a remarkable extent.
Acetylcholine ; Adenosine ; Animals ; Atropine ; Baclofen* ; Decapitation ; Exsanguination ; Hydrogen-Ion Concentration ; Myography ; Rats* ; Receptors, Muscarinic

BACKGROUND: Muscarinic receptors are distributed abundantly in the central nervous system and peripheral visceral organs, and have a close relationship with anesthesia. We investigated the effects of halothane, enflurane or isoflurane on m1 or m3 muscarinic signaling. METHODS: Using two electrode voltage clamps, Ca2+ -activated Cl- currents (ICl(Ca)) were measured in Xenopus oocytes injected with an m1 or m3 receptor mRNA. ICl(Ca) was induced with the application of acetyl beta-methylcholine with or without exposure to volatile anesthetics. RESULTS: Halothane depressed the m1 and m3 receptor function significantly (m1; 0.49 +/- 0.17 microampere -> 0.1 +/- 0.05 microampere, m3; 0.74 +/- 0.2 -> 0.23 +/- 0.06 microampere, P < 0.05). Enflurane also decreased signaling through both receptors significantly (m1; 0.49 +/- 0.1 -> 0.15 +/- 0.04 microampere, m3; 0.95 +/- 0.34 -> 0.19 +/- 0.05 microampere, P < 0.05). However, while isoflurane depressed m3 signaling significantly (0.82 +/- 0.19 -> 0.3 +/- 0.09 microampere, P < 0.05), it did not cause significant changes in ICl(Ca) through the m1 receptor (0.29 +/- 0.05 vs 0.23 +/- 0.09 microampere, P > 0.5). From a concentration-response curve, enflurane decreased m1 and m3 signaling dose-dependently. CONCLUSIONS: Our data suggests that m1 and m3 muscarinic receptors were depressed by halothane, enflurane or isoglurane except for the fact that the m1 receptor was not affected by isoflurane.
Anesthesia ; Anesthetics ; Central Nervous System ; Electrodes ; Enflurane* ; Halothane* ; Isoflurane* ; Oocytes* ; Receptors, Muscarinic* ; RNA, Messenger ; Xenopus*

BACKGROUND: The arterial baroreflex is a key mechanism for maintaining blood pressure homeostasis. Low-dose atropine (LDA) causes bradycardia, either by acting on the sinoatrial node or due to its effect on central muscarinic receptors, which increases vagal activity. We evaluated the effect of LDA on baroreflex sensitivity (BRS) in healthy awake subjects. METHODS: We assessed changes in RR interval (RRI) and systolic blood pressure (SBP), power spectral densities of heart rate variability (HRV) and systolic blood pressure variability (SBPV), and spontaneous BRS by using transfer function analysis before and after LDA (2microgram/kg) in 17 healthy volunteers. RESULTS: LDA induced not only bradycardia but also increased of the high-frequency (HF) component of HRV, RMSSD (root mean squared successive difference interval), and pNN50 (percentage of sinus cycles differing from the preceding cycle by > 50 ms). The HF and LF components of SBPV remained unchanged. Spontaneous BRS determined by transfer function analysis increased significantly (P < 0.05), and changes in BRS were significantly associated with changes in the HF component of HRV (P < 0.05). CONCLUSIONS: LDA increased vagal cardiac function and arterial baroreflex in awake subjects. This result suggests that increased vagal cardiac function by LDA application is related to baroreflex increase.
Atropine* ; Baroreflex* ; Blood Pressure ; Bradycardia ; Healthy Volunteers ; Heart Rate ; Homeostasis ; Receptors, Muscarinic ; Sinoatrial Node