Serotonergic modulation of murine fundic tone

2006 ◽  
Vol 291 (6) ◽  
pp. G1180-G1186 ◽  
Author(s):  
Lin Xue ◽  
Michael Camilleri ◽  
G. Richard Locke ◽  
Jan A. J. Schuurkes ◽  
Ann Meulemans ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Contractile Activity ◽  
Electrical Field Stimulation ◽  
Inhibitory Response ◽  
Inhibitory Input ◽  
Receptor Subtypes ◽  
Circular Smooth Muscle ◽  
Neural Input ◽  
Gr 127935

Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT1B/D receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT1B/D agonist sumatriptan contracted murine fundic muscle. The 5-HT1A receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by Nω-nitro-l-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT3 receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT4 receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT1B/D receptors. 5-HT3 receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT3 and 5-HT4 receptors modulate inhibitory neural input to murine fundic smooth muscle.

Control of human airway smooth muscle: in vitro studies

1982 ◽  
Vol 53 (5) ◽  
pp. 1080-1087 ◽  
Author(s):  
C. Davis ◽  
M. S. Kannan ◽  
T. R. Jones ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Contractile Activity ◽  
Potassium Conductance ◽  
In Vitro Study ◽  
Neural Mechanism ◽  
Electrical Field Stimulation ◽  
Inhibitory Response ◽  
Scorpion Venom ◽  
Relaxation Responses

An in vitro study of neural and myogenic control of human tracheal smooth muscle was undertaken. Over 80% of these had active tension and 13% had phasic contractile activity. Tonic and phasic activities were not reversed by indomethacin, 5,8,11,14-eicosatetraynoic acid, methysergide, mepyramine, atropine, or tetrodotoxin (TTX) but were blocked by the calcium antagonist verapamil. In some quiescent strips, tonic and/or phasic activity was induced by exposure to potassium-conductance blockers such as 4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA). Electrical (field) stimulation resulted in frequency-dependent biphasic responses: an initial atropine-sensitive cholinergic contraction followed by a nonadrenergic relaxation. This biphasic response to low stimulus parameters (less than 0.5 ms, less than 15 Hz) was blocked by TTX and scorpion venom and enhanced by 4-AP and TEA, consistent with a neural mechanism. Relaxation responses to longer pulse durations (0.5–1 ms) were not blocked by TTX despite abolition of contraction nor were they enhanced by 4-AP and TEA, suggesting a nonneural mechanism. ATP, adenosine, arachidonate metabolites, histamine, 5-hydroxytryptamine, neurotensin, or vasoactive intestinal polypeptide were ruled out as possible nonadrenergic mediators. The nature and physiological significance of the nonneural inhibitory response remains unknown.

scholarly journals Dual Excitatory and Smooth Muscle-relaxing Effect of Sideritis montana Extract on Guinea-pig Ileum

2015 ◽  
Vol 10 (3) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Barbara Tóth ◽  
Loránd Bartho ◽  
Andrea Vasas ◽  
Zsolt Sándor ◽  
Nikoletta Jedlinszki ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Electrical Field Stimulation ◽  
Inhibitory Response ◽  
Bathing Solution ◽  
Guinea Pig Ileum ◽  
Aerial Parts ◽  
Relaxing Effect

The neuronal and smooth muscle effects of a methanol extract prepared from the air-dried flowering aerial parts of Sideritis montana L. (SME) was tested in vitro on Guinea-pig ileum. The chemical composition of the investigated extract was analysed by HPLC-MS, and chrysoeriol, chlorogenic acid and caffeic acid were detected as main constituents. The isolated organ assay showed that S. montana extract caused an immediate contraction and a more slowly developing inhibitory response in the ileum. The SME-induced contractions were strongly inhibited by the acetylcholine muscarinic receptor antagonist atropine (0.5 μM), but not by either the Na+ channel blocker tetrodotoxin (TTX; 0.5 μM) or the histamine H1 receptor antagonist chloropyramine (0.5 μM). Selective desensitization of capsaicin-sensitive neurons by the sensory neuron stimulant and blocker capsaicin did not influence the contractile effect of SME. As to the spasmolytic effect, SME inhibited the effects of electrical field stimulation, exogenous acetylcholine, and histamine. These smooth muscle-relaxing effects were reversible in 40 min by repeated renewals of the bathing solution.

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

Electrophysiological analysis of responses to intrinsic nerves in circular muscle of opossum esophageal muscle

1988 ◽  
Vol 254 (1) ◽  
pp. G107-G116 ◽  
Author(s):  
R. Serio ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
High Frequency Stimulation ◽  
Organ Bath ◽  
Circular Smooth Muscle ◽  
Time To Peak ◽  
Frequency Stimulation ◽  
Sucrose Gap ◽  
Cholinergic Agents

The nerve-mediated responses to electrical field stimulation (EFS) along the opossum esophageal circular smooth muscle were studied with the sucrose-gap recording technique. Strips from 1-2, 4-5, 7-8, and 10-11 cm above the lower esophageal sphincter were stimulated with short-train (300 ms) and long-train (3 s) durations at 29 degrees C. The response always consisted of a hyperpolarization [inhibitory junction potentials (IJP)] followed by an "off depolarization" often associated with spike potentials and mechanical contraction. Proximal to distal differences in the characteristics of the evoked responses were found, i.e., increasing amplitude, duration and time to peak hyperpolarization of the IJP, increasing latency, and amplitude of the off depolarization. Neither atropine, scopolamine, physostigmine, nor guanethidine altered these characteristics substantially. Circular strips of muscularis externa, studied in the organ bath at 37 degrees C using 10-s EFS trains at 5-40 pps, produced off contractions, enhanced by physostigmine and reduced by atropine. High-frequency stimulation occasionally initiated small persistent intrastimulus ("on") responses; some were sensitive to cholinergic agents, but there was no gradient in the delay in their onset. Atropine-insensitive and tetrodotoxin-potentiated transient on responses were occasionally detected. We conclude that only the noncholinergic, nonadrenergic innervation provides a functional intrinsic innervation directly to the opossum esophagus circular smooth muscle when nerves are activated by EFS.

Effect of acute experimental colitis on rabbit colonic smooth muscle

1986 ◽  
Vol 251 (4) ◽  
pp. G538-G545 ◽  
Author(s):  
J. D. Cohen ◽  
H. W. Kao ◽  
S. T. Tan ◽  
J. Lechago ◽  
W. J. Snape
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Current Pulse ◽  
Mechanical Response ◽  
Contractile Activity ◽  
Experimental Colitis ◽  
Isometric Tension ◽  
Mucosal Inflammation ◽  
Resting Membrane Potential ◽  
Circular Smooth Muscle

The membrane potential and contractile activity of colonic circular smooth muscle from New Zealand White rabbits were studied after the production of acute experimental colitis. Colitis was induced in the distal colon by rectal infusion of formaldehyde solution, followed by an intravenous bolus of soluble immune complexes. Despite active mucosal inflammation, there are only occasional inflammatory cells in the muscularis. Electrophysiological studies on tissue from control rabbits and rabbits with colitis were performed using double sucrose gap and intracellular microelectrode techniques. The resting membrane potential was lower (-44 +/- 3 mV) in muscle from rabbits with colitis compared with control animals (-54 +/- 2 mV) (P less than 0.02). Amplitude of the electrotonic potential after a hyperpolarizing current pulse was decreased (P less than 0.05) and the time constant was shortened (P less than 0.01) in muscle from animals with colitis compared with normal animals. Amplitude (13.1 +/- 2.3 mV) and maximum rate of rise (0.24 +/- 0.06 V/s) of the spike potential, initiated by a depolarizing current pulse, were decreased in muscle from animals with colitis compared with muscle from healthy animals (P less than 0.001). Isometric tension generation after electrical and chemical depolarization of the membrane or bethanechol administration was decreased (P less than 0.001) in muscle from colitic animals. These studies suggest 1) membrane resistance and membrane potential are decreased in muscle strips from animals with colitis; and 2) there is a disturbance in the electrical and mechanical response of these tissues after stimulation.

Effect of cold temperature on membrane potential responses in opossum esophageal circular muscle

1989 ◽  
Vol 257 (4) ◽  
pp. G637-G643
Author(s):  
D. Kauvar ◽  
J. Crist ◽  
R. K. Goyal
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Cold Temperature ◽  
Resting Membrane Potential ◽  
Spike Potential ◽  
Circular Smooth Muscle ◽  
Time To Peak ◽  
Proximal Site

The effects of cold temperature on resting membrane potential (RMP) and membrane potential responses to depolarizing electrical current and intramural nerve stimulation were examined in opossum esophageal circular smooth muscle. Intracellular recordings were made in smooth muscle strips obtained from 7 to 8 cm (proximal site) and 1 to 2 cm (distal site) above the lower esophageal sphincter. RMP was not affected by changes in temperature between 34 and 22 degrees C. Cooling caused progressive inhibition of the amplitude and a slight increase in the duration of the spike potential produced by depolarizing current. Cooling did not modify the threshold for spike potential generation but decreased the spike amplitude from 34.0 +/- 0.5 mV at 34 degrees C to 14.1 +/- 2.2 mV at 22 degrees C (P less than 0.01). Electrical field stimulation with single electrical pulses (1.0 ms) produced tetrodotoxin-sensitive biphasic membrane responses consisting of initial hyperpolarization, or an inhibitory junction potential followed by depolarization that increased in amplitude as temperature was decreased from 34 to 26 degrees C and then decreased in amplitude as temperature was further decreased. At both proximal and distal sites cooling from 34 to 22 degrees C caused more than a twofold increase in the duration of hyperpolarization and time to peak depolarization. However, the increase in the absolute time of the duration of hyperpolarization and the time to peak depolarization was significantly greater at the distal than proximal esophageal site. Cooling to 16 degrees C decreased RMP and nearly abolished the biphasic membrane potential response.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exogenous ATP on canine jejunal smooth muscle

2000 ◽  
Vol 278 (5) ◽  
pp. G725-G733 ◽  
Author(s):  
L. Xue ◽  
G. Farrugia ◽  
J. H. Szurszewski
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Pyridoxal Phosphate ◽  
Electrical Field Stimulation ◽  
Muscle Cells ◽  
Disulfonic Acid ◽  
Reactive Blue 2 ◽  
Circular Smooth Muscle ◽  
Inhibitory Junction Potential ◽  
Junction Potential

Intracellular recordings were made from the circular smooth muscle cells of the canine jejunum to study the effect of exogenous ATP and to compare the ATP response to the nonadrenergic, noncholinergic (NANC) inhibitory junction potential (IJP) evoked by electrical field stimulation (EFS). Under NANC conditions, exogenous ATP evoked a transient hyperpolarization (6.5 ± 0.6 mV) and EFS evoked a NANC IJP (17 ± 0.4 mV). ω-Conotoxin GVIA (100 nM) and a low-Ca2+, high-Mg2+ solution abolished the NANC IJP but had no effect on the ATP-evoked hyperpolarization. The ATP-evoked hyperpolarization and the NANC IJP were abolished by apamin (1 μM) and N G-nitro-l-arginine (100 μM). Oxyhemoglobin (5 μM) partially (38.8 ± 5.5%) reduced the amplitude of the NANC IJP but had no effect on the ATP-evoked hyperpolarization. Neither the NANC IJP nor the ATP-evoked hyperpolarization was affected by P2 receptor antagonists or agonists, including suramin, reactive blue 2, 1-( N, O-bis-[5-isoquinolinesulfonyl]- N-methyl-l-tyrosyl)-4-phenylpiperazine, pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid, α,β-methylene ATP, 2-methylthioadenosine 5′-triphosphate tetrasodium salt, and adenosine 5′- O-2-thiodiphosphate. The data suggest that ATP evoked an apamin-sensitive hyperpolarization in circular smooth muscle cells of the canine jejunum via local production of NO in a postsynaptic target cell.

Endothelin receptor antagonists: a brief review

1994 ◽  
Vol 72 (11) ◽  
pp. 1469-1471 ◽  
Author(s):  
Suzanne Moreland
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Receptor Subtypes ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Vascular Activity ◽  
Vasodilatory Activity ◽  
Healthy Control ◽  
Circulating Levels

The endothelins are a family of potent vasoconstrictors, some of which also have vasodilatory activity. In many diseases associated with tissue hypoxia or ischemia and in diseases in which vasoconstriction plays a role, the circulating levels of endothelin are higher than in healthy, control subjects. These findings stimulated research aimed at discovering endothelin receptor antagonists. This review focuses on the binding potency and vascular activity of these new peptide and nonpeptide endothelin receptor antagonists.Key words: endothelin, endothelin receptor subtypes, vascular smooth muscle, endothelin receptor antagonist.

scholarly journals EP1- and EP3-Receptors Mediate Prostaglandin E2–Induced Constriction of Porcine Large Cerebral Arteries

2004 ◽  
Vol 24 (12) ◽  
pp. 1305-1316 ◽  
Author(s):  
Vikram Jadhav ◽  
Anthony Jabre ◽  
Shinn-Zong Lin ◽  
Tony Jer-Fu Lee
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Basilar Arteries ◽  
Cerebral Vascular

Prostaglandin E2 (PGE2) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE2-induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE2 exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE2-induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE2 and its agonists 17-phenyl trinor PGE2 (17-PGE2), sulprostone (EP1/EP3 receptor agonists), and 11-deoxy-16,16-dimethyl PGE2 (11-PGE2, an EP2/EP3-receptor agonist) induced exclusive constriction, which was not affected by endothelium denudation or cold-storage denervation of perivascular nerves. The constriction induced by PGE2, 17-PGE2, and sulprostone, but not by potassium chloride, was blocked by SC-19220 (a selective EP1-receptor antagonist), AH-6809 (an EP1/EP2-receptor antagonist), and U-73122 and neomycin (phospholipase C inhibitors). AH-6809, however, did not affect 11-PGE2–induced contraction. These results suggest that the contraction was not mediated by the EP2-receptor, but was mediated by EP1- and EP3-receptors. Furthermore, EP1-receptor immunoreactivities were found across the entire medial smooth muscle layers, whereas EP3-receptor immunoreactivities were limited to the outer smooth muscle layer toward the adventitia. Western blotting also showed the presence of EP1- and EP3-receptor proteins in cultured primary cerebral vascular smooth muscle cells. In conclusion, PGE2 exclusively constricts the adult porcine large cerebral arteries. This constriction is mediated by phosphatidyl–inositol pathway via activation of EP1- and EP3-receptors located on the smooth muscle cells. These two receptor subtypes may play important roles in physiologic and pathophysiologic control of cerebral vascular tone.

Serotonin reuptake inhibitors fluoxetine and citalopram relax intestinal smooth muscle

2001 ◽  
Vol 79 (7) ◽  
pp. 580-584 ◽  
Author(s):  
Pal Pacher ◽  
Zoltan Ungvari ◽  
Valéria Kecskeméti ◽  
Tamás Friedmann ◽  
Susanna Furst
Keyword(s):  
Smooth Muscle ◽  
Serotonin Reuptake ◽  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Electrical Field Stimulation ◽  
Intestinal Smooth Muscle ◽  
Dependent Manner ◽  
Guinea Pig Ileum ◽  
Electrical Field ◽  
Concentration Dependent Manner

Selective serotonin reuptake inhibitor antidepressants (SSRIs) exert depressant effects on cardiac myocytes and vascular smooth muscle cells by inhibiting Ca2+ channels. We hypothesized that the SSRIs fluoxetine and citalopram affect the contractile activity of intestinal smooth muscle by interfering with Ca2+ entry and (or) signaling pathways. The effects of fluoxetine and citalopram on contractions of guinea-pig ileum longitudinal muscle-myenteric plexus preparations (LMMP) were compared with the effects of the voltage-operated Ca2+ channel inhibitors nifedipine and diltiazem. In a concentration-dependent manner, nifedipine, diltiazem, fluoxetine, and citalopram elicited relaxation of LMMPs contracted by electrical field stimulation (EC50 values of 4 × 10–7 M, 1.4 × 10–6 M, 1.4 × 10–5, and 6.8 × 10–6 M, respectively). Nifedipine, diltiazem, fluoxetine, and citalopram also relaxed LMMPs contracted with a depolarizing concentration of KCl (48 mM; EC50 values of 1.8 × 10–8 M, 1.4 × 10–7 M, 3.7 × 10–6 M, and 6.3 × 10–6, respectively), a response that could be reversed by increasing the extracellular Ca2+ concentration (2.5–30 mM). These data suggest that fluoxetine and citalopram elicit relaxation of intestinal smooth muscle, likely by inhibiting Ca2+ channel(s). This effect may be of clinical importance.Key words: fluoxetine (Prozac(r)), citalopram (Seropram(r)), nifedipine, diltiazem, L-type Ca2+ channels, intestinal smooth muscle.

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