Inhibitory and excitatory mechanisms of neurotensin action in canine intestinal circular muscle in vitro

1992 ◽  
Vol 70 (10) ◽  
pp. 1423-1431 ◽  
Author(s):  
F. Christinck ◽  
E. E. Daniel ◽  
J. E. T. Fox-Threlkeld
Keyword(s):  
Potassium Channels ◽  
Muscle Contraction ◽  
Intracellular Calcium ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Membrane Resistance ◽  
Temperature Sensitive ◽  
Membrane Hyperpolarization ◽  
Neuromedin N

The effect of neurotensin on canine ileal circular muscle devoid of myenteric plexus was investigated using single and double sucrose gap techniques. Similar results were obtained with microelectrode techniques. Neurotensin caused a temperature-sensitive and dose-dependent biphasic response, an initial hyperpolarization associated with inhibition of contractile activity, followed by an excitatory phase, usually consisting of spike discharge and tonic and phasic contractions, for which depolarization was not required. Neither response was affected by tetrodotoxin, phentolamine, propranolol, or atropine. The hyperpolarization was associated with decreased membrane resistance, blocked by 10−7 M apamin, and converted to tonic depolarization by apamin (10−6 M). Tachyphylaxis to neurotensin occurred when the stimulation interval was less than 20 min. After Ca2+ depletion, depolarization was observed instead of the hyperpolarization; this depolarization was not affected by nitrendipine and was gradually abolished with repetitive stimulations at 20-min intervals. When Ca2+ was present, nifedipine did not alter the hyperpolarizing phase of the response but inhibited spiking and blocked all contractions. The excitatory phase of the response was enhanced by Bay K-8644. Neuromedin N elicited a response identical with that of neurotensin. The responses of the two peptides were completely cross tachyphylactic. Inhibitory junction potentials were not affected by neurotensin tachyphylaxis. It is concluded that neurotensin and neuromedin N activate apamin-sensitive, calcium-dependent potassium channels in circular muscle, causing membrane hyperpolarization and inhibition of muscle contraction. Release of intracellular calcium is involved in the activation of these potassium channels. When opening of potassium channels was inhibited, release of intracellular calcium caused depolarization. Neurotensin also activates L-type calcium channels, resulting in muscle contraction. Neurotensin does not appear to contribute to the compound inhibitory nerve response represented by the inhibitory junction potential.Key words: neurotensin, apamin, inhibitory junction potentials, ileum, circular muscle.

Smooth muscle mechanical responses in vitro to bethanechol after progesterone in male rat.

1978 ◽  
Vol 235 (4) ◽  
pp. E422 ◽  
Author(s):  
L A Bruce ◽  
F M Behsudi ◽  
I E Danhof
Keyword(s):  
Smooth Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Male Rat ◽  
Equal Weight ◽  
Muscarinic Agonist ◽  
Sprague Dawley ◽  
Response Curves ◽  
Dose Levels

Male Sprague-Dawley rats were pretreated subcutaneously with either progesterone (3 mg/kg per day) in a vehicle or a vehicle only for 3 days. Antral and gastroduodenal junctional tissues (GJT) were excised from both groups of animals and prepared for in vitro mechanical measurements. Responses from the circular muscle axis of these tissues were recorded with strain gauge transducers over a 30-min period. Chemical stimulation of the tissue was achieved with a muscarinic agonist, bethanechol chloride. Log-dose response curves suggested that untreated antral tissue generated stronger contractile activity than untreated GJT on an equal weight basis at bethanechol dose levels of 6.4 X 10(-6) M to 1 X 10(-4) M (P less than 0.005). Antral tissue and GJT contractile activity from the progesterone pretreated animals was significantly reduced (P less than 0.01) compared to the corresponding tissues from untreated animals at bethanechol dose levels of 6.4 X 10(-6) M and 1.28 X 10(-5) M. Progesterone pretreatment appeared to have little effect on the contractile frequency of either tissue. These results suggest possible progesteronic influences on contractile force in gastrointestinal smooth muscle.

Myogenic mechanism for peristalsis in the cat esophagus

1999 ◽  
Vol 277 (2) ◽  
pp. G306-G313 ◽  
Author(s):  
Harold G. Preiksaitis ◽  
Nicholas E. Diamant
Keyword(s):  
Muscle Contraction ◽  
Slow Wave ◽  
Circular Muscle ◽  
Smooth Muscle Contraction ◽  
Slow Waves ◽  
Mechanical Activity ◽  
Control Mechanisms ◽  
Slow Wave Oscillations

A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 μM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K+ concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves.

Differential effects of [Gln4]neurotensin on circular and longitudinal muscle of dog ileum in vitro

1987 ◽  
Vol 253 (4) ◽  
pp. G566-G572
Author(s):  
M. Karaus ◽  
K. R. Prasad ◽  
S. K. Sarna ◽  
I. M. Lang
Keyword(s):  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Differential Effects ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Muscle Contractile

We studied the effects of neurotensin analogue [Gln4]-neurotensin on isolated dog ileal longitudinal and circular muscle strips. [Gln4]neurotensin stimulated the spontaneous contractile activity of the circular muscle but inhibited that of the longitudinal muscle in a dose-dependent fashion. Hexamethonium had no effect on the spontaneous longitudinal or circular muscle contractile activity. Atropine and tetrodotoxin (TTX) both inhibited the longitudinal muscle. Atropine had no effect on the circular muscle, but TTX stimulated it. The effects of [Gln4]neurotensin on the circular muscle were reduced but not completely abolished by atropine. The inhibition of the longitudinal muscle by [Gln4]neurotensin was not reduced by any of the above antagonists but was enhanced by atropine. Electrical field stimulation (10 Hz, 100 mA) stimulated the longitudinal muscle and inhibited or stimulated the circular muscle depending on the pulse width of the stimulus. These effects were unaffected by [Gln4]neurotensin. We conclude that [Gln4]neurotensin has differential effects on isolated muscle strips of the two muscle layers in the dog ileum. It stimulates the circular muscle partially through cholinergic nerves at preganglionic sites and partially through a direct myogenic effect. [Gln4]neurotensin inhibits the spontaneous activity of the longitudinal muscle presumably by reducing the excitability of cholinergic nerves at postganglionic sites.

LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity

1999 ◽  
Vol 277 (2) ◽  
pp. G478-G486 ◽  
Author(s):  
Mark K. Eskandari ◽  
Jörg C. Kalff ◽  
Timothy R. Billiar ◽  
Kenneth K. W. Lee ◽  
Anthony J. Bauer
Keyword(s):  
Nitric Oxide ◽  
Muscle Activity ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Fold Increase ◽  
Inos Mrna ◽  
Organ Bath ◽  
Cellular Mechanisms ◽  
Circular Smooth Muscle

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time-dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitorl- N6-(1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.

Alpha 1-adrenergic receptor activation depolarizes rat supraoptic neurosecretory neurons in vitro

1986 ◽  
Vol 251 (3) ◽  
pp. R569-R574 ◽  
Author(s):  
J. C. Randle ◽  
C. W. Bourque ◽  
L. P. Renaud
Keyword(s):  
Time Course ◽  
Membrane Resistance ◽  
Receptor Activation ◽  
Membrane Hyperpolarization ◽  
Neurosecretory Neurons ◽  
Consistent Change ◽  
K Current ◽  
Supraoptic Neurons ◽  
A Current

Intracellular data were obtained from 35 supraoptic nucleus neurosecretory neurons maintained in vitro in intra-arterially perfused explants of rat hypothalamus. Addition of norepinephrine, phenylephrine, or methoxamine, but not isoproterenol (30-200 microM), consistently induced membrane depolarization, bursting activity, and an associated prolongation in action potential duration, effects that were reversibly antagonized by the alpha 1-antagonist prazosin. Norepinephrine-evoked depolarizations demonstrated no consistent change in membrane resistance and were reduced both by membrane hyperpolarization and by raising extracellular K+. Norepinephrine shortened the time course of spike hyperpolarizing afterpotentials and increased the magnitude of late depolarizing afterpotentials. It is proposed that one of norepinephrine's actions on supraoptic neurons involves K+ channels, perhaps by modulation of a transient K+ current known as A current.

scholarly journals Inhibition of Potassium Channels Affects the Ability of Pig Spermatozoa to Elicit Capacitation and Trigger the Acrosome Exocytosis Induced by Progesterone

2021 ◽  
Vol 22 (4) ◽  
pp. 1992
Author(s):  
Federico Noto ◽  
Sandra Recuero ◽  
Julián Valencia ◽  
Beatrice Saporito ◽  
Domenico Robbe ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Potassium Channels ◽  
Intracellular Calcium ◽  
Sperm Motility ◽  
Specific Inhibitor ◽  
Sperm Capacitation ◽  
Membrane Hyperpolarization ◽  
Voltage Gated ◽  
Calcium Activated Potassium Channels ◽  
Pore Domain

During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial for capacitation of mouse and human sperm, their role in pigs has not been investigated. With this purpose, sperm samples from 15 boars were incubated in capacitation medium for 300 min with quinine, a general blocker of potassium channels (including voltage-gated potassium channels, calcium-activated potassium channels, and tandem pore domain potassium channels), and paxilline (PAX), a specific inhibitor of calcium-activated potassium channels. In all samples, acrosome exocytosis was induced after 240 min of incubation with progesterone. Plasma membrane and acrosome integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and total and progressive sperm motility were evaluated after 0, 120, and 240 min of incubation, and after 5, 30, and 60 min of progesterone addition. Although blocking potassium channels with quinine and PAX prevented sperm to elicit in vitro capacitation by impairing motility and mitochondrial function, as well as reducing intracellular calcium levels, the extent of that inhibition was larger with quinine than with PAX. Therefore, while our data support that calcium-activated potassium channels are essential for sperm capacitation in pigs, they also suggest that other potassium channels, such as the voltage-gated, tandem pore domain, and mitochondrial ATP-regulated ones, are involved in that process. Thus, further research is needed to elucidate the specific functions of these channels and the mechanisms underlying its regulation during sperm capacitation.

A novel in vitro technique to study extrinsic neural control of rabbit colonic muscle and epithelial function

1993 ◽  
Vol 265 (6) ◽  
pp. G1064-G1070 ◽  
Author(s):  
J. M. Goldhill ◽  
W. H. Percy
Keyword(s):  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Neural Control ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Potential Difference ◽  
Pelvic Nerve ◽  
Sympathetic Nerve Stimulation ◽  
In Vitro Technique

A novel in vitro technique capable of simultaneously measuring distal colonic epithelial potential difference and muscle contraction is described. Under basal conditions, oscillations in both muscle tone and potential difference were observed. Pelvic nerve stimulation was shown to evoke strong "duration" contractile responses in both the longitudinal and circular muscle layers. Additionally, tonic changes in potential difference extending beyond the train of stimuli were observed, suggesting for the first time that colonic ion transport may be influenced by the pelvic nerves. However, it was unclear whether these were direct effects or indirect actions resulting from muscle contractions causing mechanical stimulation of nerves of the submucosal plexus. Lumbar colonic nerve stimulation inhibited spontaneous contractile activity and reduced basal tone in both muscle layers. However, there was no consistent effect of sympathetic nerve stimulation on transepithelial potential difference. Each of the muscle and epithelial effects of sympathetic nerve stimulation was mimicked by exogenous norepinephrine. Based on these data, it is concluded that colonic function is strongly influenced by the extrinsic innervation. Furthermore, relatively long-term modulation of epithelial function can be achieved by short bursts of pelvic nerve activity.

Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal

1997 ◽  
Vol 273 (6) ◽  
pp. G1233-G1245 ◽  
Author(s):  
G. Lu ◽  
X. Qian ◽  
I. Berezin ◽  
G. L. Telford ◽  
J. D. Huizinga ◽  
...  
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Ultrastructural Studies ◽  
Wave Characteristics ◽  
Cells Of Cajal

Inflammation suppresses phasic contractile activity in vivo. We investigated whether inflammation also suppresses in vitro phasic contractile activity and, if so, whether this could in part be due to the alteration of specific slow wave characteristics and morphology of the interstitial cells of Cajal (ICC). Circular muscle strips were obtained from normal and inflamed distal canine colon. Inflammation was induced by mucosal exposure to ethanol and acetic acid. The amplitudes of spontaneous, methacholine-induced, substance P-induced, and electrical field stimulation-induced contractions were smaller in inflamed muscle strips than in normal muscle strips. Inflammation reduced the resting membrane potential and the amplitude and duration of slow waves in circular muscle cells. Inflammation did not affect the amplitude of inhibitory junction potentials but did decrease their duration. Ultrastructural studies showed expansion of the extracellular space between circular muscle cells, reduction in the density of ICC and associated neural structures, damage to ICC processes, vacuolization of their cytoplasm, and blebbings of the plasma membrane. We conclude that inflammation-induced alterations of slow wave characteristics contribute to the suppression of phasic contractions. These alterations may, in part, be due to the damage to ICC. Inflammation impairs both the myogenic and neural regulation of phasic contractions.

Expression and effects of metabotropic CRF1 and CRF2 receptors in rat small intestine

2005 ◽  
Vol 288 (5) ◽  
pp. G1091-G1103 ◽  
Author(s):  
Christophe Porcher ◽  
Aurélie Juhem ◽  
André Peinnequin ◽  
Valérie Sinniger ◽  
Bruno Bonaz
Keyword(s):  
Small Intestine ◽  
Neural Control ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Nerve Fibers ◽  
Receptor Subtypes ◽  
Rat Small Intestine ◽  
Duodenal Motility ◽  
Functional Studies

Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1 and CRF2; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF1 and CRF2 receptors in the rat small intestine (i.e., duodenum and ileum). CRF1–2-like immunoreactivity (CRF1–2-LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF1–2-LI was found in nerve fibers of the longitudinal and circular muscle layers, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF2 than CRF1 in the ileum, whereas CRF1 expression was higher than CRF2 expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF1 antagonists (CP-154,526 and SSR125543Q) blocked CRF-like peptide-induced activation of duodenal motility but did not block CRF-like peptide-induced inhibition of ileal motility. In contrast, a CRF2 inhibitor (astressin2-B) blocked the effects of CRF-like peptides on ileal muscle contractions but did not influence CRF-like peptide-induced activation of duodenal motility. These results demonstrate the presence of CRF1–2 in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1 receptor while inhibiting phasic contractions of the ileum through CRF2 receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of small intestinal motility through CRF receptors.

Neuronal Inhibition Determines the Gastrointestinal Motor State

Physiology ◽  
1996 ◽  
Vol 11 (2) ◽  
pp. 67-71 ◽  
Author(s):  
DS Delbro
Keyword(s):  
Contractile Activity ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Blocking Agent ◽  
Myenteric Neurons ◽  
Circular Muscle Layer ◽  
Neuronal Inhibition ◽  
Gastrointestinal Motor

The nerve-blocking agent tetrodotoxin induces contractile activity of the gut circular muscle, in vitro, and intestinal hypermotility, in vivo. According to an hypothesis put forward more than 20 years ago, the circular muscle layer is tonically suppressed due to spontaneously active myenteric neurons that "drive" inhibitory motoneurons to the muscle.

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