Prostaglandins and myogenic control of tension in lower esophageal sphincter

Daniel, E. E.; Crankshaw, J.; Sarna, Sushil K.

doi:10.1016/0090-6980(79)90014-5

Cited by 22 publications

(14 citation statements)

References 14 publications

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“…In different systems, these three substances are known to activate RhoA/ ROCK via the G protein-coupled receptors (GPCRs) AT 1 -R, TXA2 receptor (TPR), and PGF 2␣ receptor (FPR), respectively (1,50). Recent studies from different laboratories have demonstrated the role of RAS (8,21,33,48) and AA pathways in the contractility of the human gastrointestinal smooth muscle (5,11,13,24). However, to our knowledge, there have been no published data demonstrating the role of RAS and AA pathway on basal muscular tone in human IAS.…”

mentioning

confidence: 99%

Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

Rattan

Singh

Kumar

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ~80% decrease in the IAS tone, whereas that of RAS lead to ~20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS.

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confidence: 99%

Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

Rattan

Singh

Kumar

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Furthermore, the RMP of LES muscle is relatively more positive (B À41 mV) compared to the adjacent oesophageal body (B À54 mV) (Daniel et al, 1976;Jury et al, 1992;Conklin et al, 1993;Zhang et al, 2000;Zhang and Paterson, 2003), which results in on-going spike-like action potentials, due to continuous Ca 2 þ influx through voltage-sensitive Ca 2 þ channels (Kubota et al, 1998;Zhang et al, 2000). In the current study, we recorded an RMP of B À43 mV, which is comparable to that recorded in guinea-pig (Yuan et al, 1998;Yuan and Brookes, 1999) and opossum LES (Daniel et al, 1976;Zhang et al, 2000). It is also similar to that recorded in mouse LES by Imaeda and Cunnane (2003), but quite different from that reported by (C(a-c) and D(a-c)) IJPs before, 10 min after application of NFA and 10 min after wash out in clasp and sling muscles, respectively The effects of NFA were reversible.…”

Section: Discussionmentioning

confidence: 94%

“…Maintenance of basal tone in opossum LOS is mainly dependent on influx of extracellular Ca 2+ via nifedipine‐sensitive (L‐type) Ca 2+ channels ( Fox and Daniel, 1979 ; Zhang et al , 2000 ). Furthermore, the RMP of LES muscle is relatively more positive (∼ −41 mV) compared to the adjacent oesophageal body (∼ −54 mV) ( Daniel et al , 1976 ; Jury et al , 1992 ; Conklin et al , 1993 ; Zhang et al , 2000 ; Zhang and Paterson, 2003 ), which results in on‐going spike‐like action potentials, due to continuous Ca 2+ influx through voltage‐sensitive Ca 2+ channels ( Kubota et al , 1998 ; Zhang et al , 2000 ). In the current study, we recorded an RMP of ∼ −43 mV, which is comparable to that recorded in guinea‐pig ( Yuan et al , 1998 ; Yuan and Brookes, 1999 ) and opossum LES ( Daniel et al , 1976 ; Zhang et al , 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Regional differences in nitrergic innervation of the smooth muscle of murine lower oesophageal sphincter

Zhang

Mashimo

Paterson

2008

British J Pharmacology

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Background and purpose: Anatomical and pharmacological studies have demonstrated that the lower oesophageal sphincter (LES) is not a simple homogenous circular muscle with uniform innervation. Regional differences have been demonstrated in several species including humans. We investigated, for the first time in mice LES, regionally distinct physiological and pharmacological characteristics of the neuromusculature. Experimental approach: Conventional intracellular recordings and pharmacological techniques were employed to evaluate electrical properties and functional innervation of smooth muscle cells. Results from CD1 (control), nNOS (À/À) and eNOS (À/À) genetic knockout mice were compared. Key results: Smooth muscle of sling and clasp LES displayed unitary membrane potentials of 1-4 mV. Transmural nerve stimulation produced a monophasic inhibitory junction potential (IJP) in the sling, whereas in the clasp a biphasic IJP, consisting of a brief IJP followed by a long-lasting slow IJP (lsIJP), was induced. Pharmacological interventions and genetically modified mice were used to demonstrate a monophasic apamin-sensitive (purinergic) component in both LES regions. However, the nitrergic IJP was monophasic in the sling and biphasic in the clasp. Unitary membrane potentials and IJPs were not different in CD1 and eNOS (À/À) mice, suggesting no involvement of myogenic NOS. Conclusion and implications: These data in mouse LES indicate that there are previously unreported regional differences in the IJP and that both the apamin-resistant monophasic and biphasic IJPs are mediated primarily by nitrergic innervation.

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“…Thus in contrast to Burleigh (1979) we suggest that truly sphincteric muscle may be identified by its ability to develop very high levels of tone rather than its inability to produce an after-contraction. Inherent myogenic tone is likewise a property of the opossum lower oesophageal sphincter (Daniel, Taylor & Holman, 1976). Isometric muscle strips from the human internal anal sphincter share this property of substantial myogenic tone with muscle from the region of the o.gj.…”

Section: Discussionmentioning

confidence: 99%

Effect of Drugs and Electrical Field Stimulation on Circular Muscle Strips From Human Lower Oesophagus

McKirdy¹,

Marshall²

1985

Exp Physiol

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SUMMARYSphincteric muscle from human lower oesophagus may be identifiable in vitro by its ability to develop a very high level of tone (sustained resting tension). Circular muscle strips from human lower oesophagus generally behave in a similar manner to strips from the opossum oesophagus with respect to development of tone, responses to electrical field stimulation and responses to a variety of drugs. Pharmacological analysis of responses to field stimulation in strips from the region of the oesophago-gastric junction suggests that thF typical biphasic response (relaxation followed by an after-contraction) is mediated by nerves which are neither adrenergic nor cholinergic. Of the substances examined only vasoactive intestinal peptide (VIP) cannot be excluded as a possible candidate for the role of inhibitory transmitter. The mechanism producing the after-contraction is not clear but it would seem unlikely that this is simply a rebound contraction. The after-contraction can be blocked independently of the relaxation by a variety of agents and is potentiated by metoclopramide.

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Prostaglandins and myogenic control of tension in lower esophageal sphincter

Cited by 22 publications

References 14 publications

Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

Regional differences in nitrergic innervation of the smooth muscle of murine lower oesophageal sphincter

Effect of Drugs and Electrical Field Stimulation on Circular Muscle Strips From Human Lower Oesophagus

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