Differential inflammatory modulation of canine ileal longitudinal and circular muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. G341-G350 ◽  
Author(s):  
Xuan-Zheng Shi ◽  
Sushil K. Sarna

The aim of this study was to identify the subtypes of muscarinic receptors that mediate in vivo and in vitro canine ileal longitudinal muscle contractions and whether their role is modulated by inflammation. Previous studies have reported that circular muscle contractions are suppressed in ileal inflammation induced by mucosal exposure to ethanol and acetic acid. We found that inflammation had no significant effect on in vivo and in vitro spontaneous or muscarinic receptor-mediated contractions of the longitudinal muscle. The longitudinal muscle contractions were mediated primarily by the M3 receptor subtype. However, the IC50 of the M2 receptor antagonist methoctramine was only 10 times greater than that of the M3 receptor antagonist 4-DAMP in the longitudinal muscle, whereas it was 224 times greater in the circular muscle. M2receptor-coupled decrease of intracellular cAMP occurred in the longitudinal but not in the circular muscle from the normal ileum. Inflammation did not alter this coupling in the longitudinal muscle but established it in the circular muscle. In conclusion, M2 receptors may play a greater role in the mediation of longitudinal muscle contractions than circular muscle contractions. Inflammation does not alter the contractility or the relative role of muscarinic receptor subtypes in longitudinal muscle cells. However, it modulates the M2 receptor coupling to adenylate cyclase in the circular muscle.

1992 ◽  
Vol 73 (5) ◽  
pp. 2069-2073 ◽  
Author(s):  
J. Mullol ◽  
J. N. Baraniuk ◽  
C. Logun ◽  
M. Merida ◽  
J. Hausfeld ◽  
...  

Mucus glycoproteins (MGP) are high-molecular-weight glycoconjugates that are released from submucosal glands and epithelial goblet cells in the respiratory tract. Muscarinic receptors have an important role in the regulation of human nasal glandular secretion and mucus production, but it is not known which of the five muscarinic receptor subtypes are involved. The effect of nonselective and M1-, M2-, and M3-selective muscarinic antagonists on methacholine (MCh)-induced MGP secretion from human nasal mucosal explants was tested in vitro. MGP was assayed by enzyme-linked immunosorbent assay using a specific anti-MGP monoclonal antibody (7F10). MCh (100 microM) induced MGP secretion up to 127% compared with controls. MCh-induced MGP release was significantly inhibited by atropine (100 microM), the M, receptor antagonist pirenzepine (10–100 microM), and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 1–100 microM). 4-DAMP significantly inhibited MCh-induced MGP release at a lower concentration (1 microM) than pirenzepine (10 microM). The M2 receptor antagonists AF-DX 116 and gallamine (both at 100 microM) had no effect. No antagonist alone had a significant effect on MGP release. These results indicate that the M1 and M3 muscarinic receptor subtypes regulate MGP secretion from human nasal mucosa and suggest that the M3 receptor has the predominant effect.


2004 ◽  
Vol 24 (12) ◽  
pp. 1305-1316 ◽  
Author(s):  
Vikram Jadhav ◽  
Anthony Jabre ◽  
Shinn-Zong Lin ◽  
Tony Jer-Fu Lee

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.


1984 ◽  
Vol 62 (10) ◽  
pp. 1304-1314 ◽  
Author(s):  
E. E. Daniel ◽  
Y. Sakai ◽  
J. E. T. Fox ◽  
V. Posey-Daniel

The structural relationship of nerve, muscle, and interstitial ceils of Cajal in circular muscle of the lesser curvature of the dog stomach (corpus) has been studied. This muscle has also been characterized functionally. Muscle cells are arranged in bundles and are interconnected by numerous gap junctions averaging 30 per 100 cross-sectioned muscle cells, and leading to an estimate that each cell has about 200 gap junctions. No other smooth muscle studied to date has such a high density of gap junctions. Nerve varicosities, mostly containing a predominance of small agranular vesicles with some containing a predominance of large granular vesicles, are located outside muscle bundles, usually in small- to medium-sized bundles. Very few nerves containing small granular vesicles, presumably adrenergic, were found in agreement with functional studies. A substantial number of damaged nerve profiles was also found, perhaps contributing to the loss of nerve-dependent responses present in vivo, but absent in vitro. Interstitial cells of Cajal were rare in this tissue, about 1 per 1000 cross-sectioned muscle cells. When present, they often made gap junction contact with smooth muscle and were closely innervated. The findings of a structural basis for very tight coupling between cells, the absence of a structural basis for direct neural control over motor function, and other findings have implications for the control of contractions in this muscle.


2017 ◽  
Vol 32 (2) ◽  
pp. 101-108
Author(s):  
Kumiko Dojo ◽  
Yoshiaki Yamaguchi ◽  
Jean-Michel Fustin ◽  
Masao Doi ◽  
Masaki Kobayashi ◽  
...  

Among nonphotic stimulants, a classic cholinergic agonist, carbachol, is known to have a strong and unique phase-resetting effect on the circadian clock: Intracerebroventricular carbachol treatment causes phase delays during the subjective early night and phase advances in the subjective late night, but the effects of this drug on the suprachiasmatic nucleus (SCN) in vivo and in vitro are still controversial. In the present study, we succeeded in reproducing the biphasic phase-shifting effect of carbachol on clock gene expression in organotypic SCN slices prepared from mice carrying a Per1-promoter fused luciferase gene ( Per1-luc). Since this biphasic effect of carbachol in Per1-luc SCN was prevented by atropine but not by mecamylamine, we concluded that these phase shifts were muscarinic receptor–dependent. Next, we analyzed the expression of muscarinic receptors in the SCN by in situ hybridization and found that M3 and M4 subtypes were expressed in SCN cells. These signals appeared neonatally and reached adult levels at postnatal day 10. Together, these findings suggest that carbachol has a phase-dependent phase-shifting effect on the SCN clock through muscarinic receptor subtypes expressed in the SCN.


1990 ◽  
Vol 258 (1) ◽  
pp. G164-G170 ◽  
Author(s):  
J. Ren ◽  
K. Schulze-Delrieu

We investigated whether the contractions of the isolated smooth muscle opossum esophagus can propel luminal contents. Wax particles were placed into the esophagus in vitro, and esophageal contractions were evoked by stimulating either primarily the intrinsic esophageal nerves (using electrical pulses of 0.5 ms) or the esophageal muscle directly (using pulses of 0.5 s). Direct muscle stimulation and neural stimulation produced circular muscle contractions of similar amplitude, but only neural stimulation was associated with a propagating ring contraction and longitudinal muscle contraction. Movement of the wax particle occurred after 21% of all stimulus responses. Aborad movement of the wax particle was 10 times as common as was its orad movement. Wax movement occurred less commonly and over shorter distance with muscle as compared with neural stimulation. The distance the wax moved was enhanced when the esophagus was allowed to shorten in its longitudinal axis. Movement occurred late during the contraction response and at velocities less than that of the ring contraction. Also, the ring contraction passed over the particle. The amplitude of circular muscle contractions had no predictive value for the occurrence of propulsion. The finding that the isolated esophagus can propel luminal contents in the aborad direction supports the thesis that peristalsis is primarily a function of the intrinsic neuromuscular organization of the smooth muscle esophagus.


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