Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian Brush-tailed Possum

Author(s):  
RobertA. Baker ◽  
GinoT.P. Saccone ◽  
David Costi ◽  
Anders Thune ◽  
James Toouli
1985 ◽  
Vol 249 (5) ◽  
pp. G572-G579
Author(s):  
J. F. Helm ◽  
W. J. Dodds ◽  
J. Christensen ◽  
S. K. Sarna

We evaluated the control mechanism of peristaltic contractions in the opossum sphincter of Oddi (SO) by means of an in vitro preparation. At each of four sites spaced uniformly along the sphincter segment, a force transducer recorded contractions while a monopolar electrode recorded myoelectric activity. Spontaneous myoelectric and contractile activity occurred in 15 of the 20 intact SO specimens studied. Electrical recordings showed characteristic control waves and response activity. Each control wave was invariably accompanied by a phasic contraction, irrespective of whether or not response activity was superimposed on the control wave. The predominant motor activity of the SO was antegrade peristalsis. Retrograde peristalsis occurred when antegrade peristalsis failed to traverse the entire sphincter. Spontaneous SO phasic contractions were not antagonized by tetrodotoxin. Muscle rings sectioned from the SO exhibited spontaneous phasic contractions with a proximal-to-distal gradient of intrinsic contraction frequencies. We conclude that a) the frequency of SO phasic contractions is determined by control wave frequency, b) spontaneous SO peristalsis is myogenic in origin and may be modeled by a linear array of bidirectionally coupled relaxation oscillators, c) the predominance of antegrade peristalsis may be explained by a high-frequency oscillator in the proximal SO that drives the slower, more distal oscillators, d) retrograde peristalsis is initiated by an ectopic oscillator in the distal SO when antegrade contractions fail to propagate the entire length of the SO, and e) ectopic SO contractions can propagate retrograde when the more proximal oscillators are not in their absolutely refractory state.


1990 ◽  
Vol 258 (1) ◽  
pp. G138-G142 ◽  
Author(s):  
R. Calabuig ◽  
M. G. Ulrich-Baker ◽  
F. G. Moody ◽  
W. A. Weems

This study investigates whether the phasic contractions of the opossum sphincter of Oddi (SO) delay bile flow by acting as a resistor or facilitate bile flow by acting as a pump. The common bile duct (CBD) and an adjacent segment of duodenum from eight opossums were studied in a propulsion evaluation system in vitro. This system required the production of hydrostatic work by the SO to transfer fluid from the CBD to the duodenum when the pressure in the duodenum was equal or greater than the pressure in the CBD. Fluid movement from the CBD to duodenum and duodenum to CBD was studied at pressure gradients up to 50 cmH2O before and after sodium nitroprusside (10(-7) M) inhibition of smooth muscle contractile activity. All preparations propelled fluid from the CBD to the duodenum against a pressure gradient ranging from 10 to 50 cmH2O. The SO emptied the CBD in a monoexponential fashion, with a time constant of 1.52 +/- 0.7 min, until CBD pressure was reduced to 8.5 +/- 3.2 cmH2O, when propulsion ceased. Superimposed on the CBD pressure waveform were pressure pulses of 1-2 cmH2O in amplitude that resulted from the contractions of the SO. CBD pressure was higher at the start than at the end of a periodic pressure pulse, whereas CBD pressure was stable between pulses. The frequency of the pressure pulses was greatest at the maximal CBD pressure (9.4/min) and decreased significantly when the basal pressure was reached (1.5/min, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


2012 ◽  
Vol 302 (1) ◽  
pp. C141-C153 ◽  
Author(s):  
Susan G. Dorsey ◽  
Richard M. Lovering ◽  
Cynthia L. Renn ◽  
Carmen C. Leitch ◽  
Xinyue Liu ◽  
...  

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.


2002 ◽  
Vol 63 (12) ◽  
pp. 1687-1694 ◽  
Author(s):  
Marc Zulauf ◽  
Cecile Spring ◽  
Richard Eicher ◽  
Mireille Meylan ◽  
Gaby Hirsbrunner ◽  
...  
Keyword(s):  

2002 ◽  
Vol 283 (6) ◽  
pp. H2268-H2275 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Naomi C. Chesler ◽  
Lisa Vitullo ◽  
Marilyn J. Cipolla

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.


1978 ◽  
Vol 235 (4) ◽  
pp. E422 ◽  
Author(s):  
L A Bruce ◽  
F M Behsudi ◽  
I E Danhof

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.


2003 ◽  
Vol 284 (2) ◽  
pp. G213-G220 ◽  
Author(s):  
W. H. Percy ◽  
T. H. Fromm ◽  
C. E. Wangsness

This in vitro study tested the hypothesis that muscularis mucosae contractile activity contributes to rabbit colonic mucosal function by mechanisms other than simple mechanical deformation of the epithelium. Experiments were performed by using a technique that allows simultaneous recording of muscle activity and transmucosal potential difference, a measure of epithelial ion transport. ATP, bradykinin, histamine, PGE2, PGF1α, and PGF2α elicited muscularis mucosae contractions that were resistant to atropine and TTX. Only ATP-induced contractions were indomethacin sensitive, and only those to dimethylphenylpiperazinium iodide (DMPP) were reduced by atropine. All agonist-evoked increases in transmucosal potential difference were atropine resistant, and, with the exception of those to PGE2, PGF2α, and VIP, they were also TTX sensitive. Mucosal responses to ATP, bradykinin, and histamine were indomethacin sensitive, whereas those to DMPP, the prostaglandins, and VIP were not. When cyclooxygenase activity or the mucosal innervation was compromised, even maximal muscularis mucosae contractions did not produce large secretory responses. It is concluded that contraction-related prostaglandin synthesis and noncholinergic secretomotor neuron stimulation represent the physiological transduction mechanism through which muscularis mucosae motor activity is translated into mucosal secretion.


1986 ◽  
Vol 103 (6) ◽  
pp. 2153-2161 ◽  
Author(s):  
L C Cerny ◽  
E Bandman

The expression of neonatal myosin heavy chain (MHC) was examined in developing embryonic chicken muscle cultures using a monoclonal antibody (2E9) that has been shown to be specific for that isoform (Bandman, E., 1985, Science (Wash. DC), 227: 780-782). After 1 wk in vitro some myotubes could be stained with the antibody, and the number of cells that reacted with 2E9 increased with time in culture. All myotubes always stained with a second monoclonal antibody that reacted with all MHC isoforms (AG19) or with a third monoclonal antibody that reacted with the embryonic but not the neonatal MHC (EB165). Quantitation by ELISA of an extract from 2-wk cultures demonstrated that the neonatal MHC represented between 10 and 15% of the total myosin. The appearance of the neonatal isoform was inhibited by switching young cultures to medium with a higher [K+] which has been shown to block spontaneous contractions of myotubes in culture. Furthermore, if mature cultures that reacted with the neonatal antibody were placed into high [K+] medium, neonatal MHC disappeared from virtually all myotubes within 3 d. The effect of high [K+] medium was reversible. When cultures maintained in high [K+] medium for 2 wk were placed in standard medium, which permitted the resumption of contractile activity, within 24 h cells began to react with the neonatal specific antibody, and by 72 h many myotubes were strongly positive. Since similar results were also obtained by inhibiting spontaneous contractions with tetrodotoxin, we suggest that the development of contractile activity is not only associated with the maturation of myotubes in culture, but may also be the signal that induces the expression of the neonatal MHC.


1996 ◽  
Vol 199 (11) ◽  
pp. 2359-2367
Author(s):  
C Brösamle ◽  
D P Kuffler

The vertebrate neuromuscular junction is a highly specialized structure containing many unique proteins and an underlying cluster of nuclei. Part of this specialization results from the expression of the genes for these proteins in nuclei clustered in the postsynaptic region. Contractile activity, as well as molecules located in the synaptic extracellular matrix (ECM), have been implicated in the induction of gene expression in these clustered nuclei. The present experiments were aimed at examining whether the presence of the synaptic ECM and presynaptic cells play a role in maintaining the clustering of the nuclei. We describe the normal distribution of nuclei clustered in the synaptic region of intact adult frog, Rana pipiens, skeletal muscle fibers and show that innervation is not required to maintain the nuclear clusters. Even after long-term (4 week) denervation, the clusters remain unchanged. Dissociation of the muscle fibers with proteases that remove ECM, Schwann cells and other satellite cells from the synaptic sites is followed by a rapid (within approximately 1.5 h) and almost complete dispersal of the clustered nuclei. Attempts to recluster the postsynaptic nuclei by the application of ECM components to muscle fibers in vitro were not successful. We propose that a factor or factors, localized in the synaptic ECM as a result of synapse formation and acting via the transmembrane or cytoplasmic domains of their respective receptors, induces the formation of a specialized cytoskeleton in the postsynaptic region that is capable of pulling in or 'trapping' nuclei. The removal of these factors from the ECM by proteases brings about the disorganization of the cytoskeleton and the freeing of the 'trapped' nuclei.


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