Influence of purinoceptors' agonists and antagonists on opossum internal anal sphincter

1988 ◽  
Vol 255 (3) ◽  
pp. G389-G394 ◽  
Author(s):  
S. Rattan ◽  
R. Shah
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Inhibitory Effect ◽  
Inhibitory Response ◽  
Rectal Balloon ◽  
Balloon Distension ◽  
Before And After ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

Studies were performed in alpha-chloralose-anesthetized and pancuronium-treated opossums. Resting internal anal sphincter pressures (IASP) were monitored using low-compliant continuously perfused catheters. P1 and P2 purinoceptor agonists, adenosine and ATP, respectively, administered close intra-arterially, caused dose-dependent decreases in the IASP. The inhibitory effect of these agonists on the IASP was tetrodotoxin resistant. Rectal balloon distension (RD) (which mimics the rectoanal inhibitory reflex) caused volume-dependent IAS relaxation. Electrical stimulation of the sacral nerve (SNS) also produced frequency-dependent decreases in IASP. The inhibitory response to adenosine (P1 purinoceptor agonist), ATP (P2 purinoceptor agonist), RD, and SNS on the internal anal sphincter (IAS) was examined before and after 8-phenyltheophylline (P1 purinoceptor antagonist) and alpha,beta-methylene ATP (P2 purinoceptor antagonist that irreversibly binds and desensitizes P2 purinoceptor). P1 and P2 purinoceptor antagonists produced selective antagonism of the inhibitory responses on the IAS of their respective agonists only. Furthermore, high doses of adenosine and ATP produced desensitization and block of their own actions only. The purinoceptors' antagonists, and the desensitization of purinoceptors by high doses of adenosine and ATP, failed to modify the fall in IASP in response to RD or SNS. From these studies we conclude that distinct inhibitory P1 and P2 purinoceptors are present on the IAS smooth muscle. However, these inhibitory purinoceptors may not be responsible for the rectoanal reflex-mediated IAS relaxation.

scholarly journals RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

2012 ◽  
Vol 302 (7) ◽  
pp. G664-G675 ◽  
Author(s):  
Satish Rattan ◽  
Jagmohan Singh
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Control Mechanisms ◽  
Rock Inhibitor ◽  
Critical Determinant ◽  
Molecular Control ◽  
Motility Disorders ◽  
Basal Tone ◽  
Before And After ◽  
Rational Therapy

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8to 10−4M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats

1995 ◽  
Vol 269 (3) ◽  
pp. R662-R668 ◽  
Author(s):  
T. Ando ◽  
T. Ichijo ◽  
T. Katafuchi ◽  
T. Hori
Keyword(s):  
Prostaglandin E2 ◽  
Sympathetic Nerve ◽  
Time Course ◽  
Sympathetic Nerve Activity ◽  
Dependent Manner ◽  
Central Administration ◽  
Nerve Activity ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

The effects of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in urethan- and alpha-chloralose-anesthetized rats. An intra-third-cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega-trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic SNA, with a time course similar to that of PGE2-induced responses. In contrast, EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1 agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg). Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10 nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic SNA through its action on EP1 receptors.

CGRP and ANF cause relaxation of opossum internal anal sphincter via different mechanisms

1991 ◽  
Vol 260 (5) ◽  
pp. G764-G769 ◽  
Author(s):  
S. Rattan ◽  
C. Moummi ◽  
S. Chakder
Keyword(s):  
Smooth Muscle ◽  
Anal Sphincter ◽  
Cyclic Nucleotides ◽  
Internal Anal Sphincter ◽  
Camp Content ◽  
Calcitonin Gene ◽  
Before And After ◽  
Camp And Cgmp

This investigation examined and compared the role of cyclic nucleotides in the mediation of internal anal sphincter (IAS) relaxation caused by the addition of neuropeptide calcitonin gene-related peptide (CGRP) and atrial natriuretic factor (ANF). The studies were performed in vitro on smooth muscle strips of opossum IAS. The relaxation produced by CGRP and ANF was examined before and after the addition of tetrodotoxin (TTX) (1 x 10(-6)M). At this concentration, TTX did not have any significant effect on the relaxation produced by either CGRP or ANF, suggesting that these peptides act directly on the smooth muscle. Addition of CGRP (3 x 10(-6) M) produced the maximal relaxation and significantly increased cAMP content without changing cGMP. On the other hand, addition of ANF (3 x 10(-6) M) caused a similar fall in IAS tension that was accompanied by a significant elevation in cGMP without any change in cAMP content. The rises in the levels of cyclic nucleotides preceded the onset of fall in the resting tension of IAS. Our results demonstrate that CGRP and ANF relax isolated strips of opossum IAS by their action directly at the smooth muscle and that this relaxation is associated with an increase in cAMP and cGMP, respectively. The studies suggest the presence of both cAMP and cGMP pathways in the IAS and that the relaxation of IAS smooth muscle in response to different peptides may occur via a specific intracellular biochemical pathway.

Inhibitory effect of CO on internal anal sphincter: heme oxygenase inhibitor inhibits NANC relaxation

1993 ◽  
Vol 265 (4) ◽  
pp. G799-G804 ◽  
Author(s):  
S. Rattan ◽  
S. Chakder
Keyword(s):  
Smooth Muscle ◽  
Anal Sphincter ◽  
Heme Oxygenase ◽  
Nerve Stimulation ◽  
Internal Anal Sphincter ◽  
Direct Action ◽  
Second Messengers ◽  
Protoporphyrin Ix ◽  
Zinc Protoporphyrin ◽  
Before And After

We examined the effect and role of CO in opossum internal anal sphincter (IAS) relaxation in response to nonadrenergic noncholinergic (NANC) nerve stimulation. Effects of NANC nerve stimulation on the IAS tension and second messengers (cAMP and cGMP) were examined before and after the selective heme oxygenase (HO) inhibitor zinc protoporphyrin IX (Zn PP-IX). The HO activity of the IAS smooth muscle was determined before and after NANC nerve stimulation. CO caused a concentration-dependent and tetrodotoxin-resistant fall in the resting tension of the IAS. The direct action of CO was confirmed by its relaxant action on the isolated smooth muscle cells. Furthermore, CO caused an increase in the tissue cGMP levels comparable to that observed with nerve stimulation. Zn PP-IX caused suppression of IAS relaxation caused by NANC nerve stimulation and vasoactive intestinal polypeptide (VIP) but not by peptide histidine-isoleucine and suppression of the increase in cGMP in response to NANC nerve stimulation. Zn PP-IX had no significant effect on the IAS responses to CO, nitric oxide (NO), and the beta-adrenoceptor agonist isoproterenol. The IAS responses to CO were not modified by the NO synthase inhibitor NG-nitro-L-arginine. Significant HO activity was detected in the IAS, which increased further in response to NANC nerve stimulation and VIP. The direct relaxant actions of CO and the suppression of NANC-mediated relaxation of the IAS by the HO inhibitor suggest the involvement of CO in the neurally mediated IAS relaxation.

Influence of sacral nerves on the internal anal sphincter of the opossum

1987 ◽  
Vol 253 (3) ◽  
pp. G345-G350
Author(s):  
S. Rattan ◽  
R. Shah
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Nicotinic Receptors ◽  
Inhibitory Neurons ◽  
Inhibitory Pathway ◽  
Release Of Acetylcholine ◽  
Adrenergic Antagonists ◽  
Sacral Nerves ◽  
Alpha Chloralose ◽  
Stimulation Of

The purpose of the present studies is to 1) compare the effects of stimulation of different sacral nerves (S1-S5) on internal anal sphincter (IAS) pressures and 2) examine the nature of synaptic transmission in the sacral inhibitory pathway to the IAS. Pressures from the IAS of alpha-chloralose-anesthetized opossums were recorded using a low-compliance continuously perfused catheter assembly. Electrical stimulation of the third and fourth sacral nerves (S3 and S4) caused frequency-dependent IAS relaxation, whereas stimulation of other sacral nerves was without significant effect on the IAS. Relaxation of the IAS in response to S4 stimulation was not significantly modified by atropine, pirenzepine dihydrochloride, hexamethonium chloride, or adrenergic antagonists. However, a combination of either atropine and hexamethonium or pirenzepine and hexamethonium caused a significant antagonism of sacral nerve-stimulated relaxation without modifying the inhibitory responses of local transmural nerve stimulation and isoproterenol. From these studies we conclude that 1) in the opossum the sacral nerves primarily exert inhibitory influences on the IAS and 2) the sacral inhibitory pathway involves the release of acetylcholine from preganglionic fibers, which in turn causes the activation of both muscarinic (M1) and nicotinic receptors on postganglionic, noncholinergic, nonadrenergic inhibitory neurons.

Effect of porcine follicular fluid preparations on gonadotrophin secretion by the mouse pituitary gland in vitro

1983 ◽  
Vol 96 (1) ◽  
pp. 73-84 ◽  
Author(s):  
K. Kato ◽  
M. R. Sairam ◽  
K. Ramasharma
Keyword(s):  
Follicular Fluid ◽  
Inhibitory Effect ◽  
Gonadotrophin Secretion ◽  
Before And After ◽  
Pituitary Glands ◽  
Continuous Presence ◽  
High Doses ◽  
Mouse Pituitary ◽  
Lh Rh

The acute effects of pooled porcine follicular fluid (PFF), before and after various methods of processing to eliminate steroids, were studied on the luteinizing hormone releasing hormone (LH-RH)-induced release of FSH and LH by whole pituitary glands, from 34-day-old mice, incubated in vitro for 3–4 h. Charcoal treatment of PFF eliminated the steroids and reduced the inhibitory potency on gonadotrophin secretion. On the other hand, dialysis or ultrafiltration (mol. wt > 10 000) did not reduce the inhibitory activity on gonadotrophin secretion. Of the three steroids tested, only oestradiol at a concentration of 10−10 mol/l inhibited FSH and LH secretion in vitro. This inhibitory effect was counteracted by the inclusion of the oestrogen antagonist tamoxifen in the incubation medium. The presence of tamoxifen did not decrease the suppression of FSH and LH induced by PFF, suggesting that the inhibition observed under the conditions of incubation was not due to oestrogen. Preincubation of mouse pituitary tissue for 1 h with PFF reduced the subsequent release of bioactive FSH and LH induced by LH-RH. The inhibitory effect of PFF was rapid and sustained. The continuous presence of PFF throughout the incubation period was not necessary for manifestations of the inhibitory effects on gonadotrophin release. The suppression of gonadotrophin secretion was related to the dose of PFF with the curve showing a biphasic pattern. The degree of FSH suppression was uniformly greater than that of LH, showing the preferential nature of the inhibitory effect of PFF. At high doses of PFF, the degree of FSH suppression was decreased significantly. This effect on LH release was less pronounced. The inhibition caused by PFF in the in-vitro incubation procedure was not due to destruction of LH-RH or the released gonadotrophins.

scholarly journals Heme oxygenase-1 upregulation modulates tone and fibroelastic properties of internal anal sphincter

2014 ◽  
Vol 307 (6) ◽  
pp. G595-G601 ◽  
Author(s):  
Chadalavada Vijay Krishna ◽  
Jagmohan Singh ◽  
Sumit Kumar ◽  
Satish Rattan
Keyword(s):  
Anal Sphincter ◽  
Heme Oxygenase ◽  
Internal Anal Sphincter ◽  
Protoporphyrin Ix ◽  
Rho Kinase ◽  
Electrical Field Stimulation ◽  
Heme Oxygenase 1 ◽  
Expression Levels ◽  
Age Related ◽  
Before And After

A compromise in the internal anal sphincter (IAS) tone and fibroelastic properties (FEP) plays an important role in rectoanal incontinence. Herein, we examined the effects of heme oxygenase (HO)-1 upregulation on these IAS characteristics in young rats. We determined the effect of HO-1 upregulator hemin on HO-1 mRNA and protein expressions and on basal IAS tone and its FEP before and after HO-1 inhibitor tin protoporphyrin IX. For FEP, we determined the kinetics of the IAS smooth muscle responses, by the velocities of relaxation, and recovery of the IAS tone following 0 Ca2+ and electrical field stimulation. To characterize the underlying signal transduction for these changes, we determined the effects of hemin on RhoA-associated kinase (RhoA)/Rho kinase (ROCK) II, myosin-binding subunit of myosin light chain phosphatase 1, fibronectin, and elastin expression levels. Hemin increased HO-1 mRNA and protein similar to the increases in the basal tone, and in the FEP of the IAS. Underlying mechanisms in the IAS characteristics are associated with increases in the genetic and translational expressions of RhoA/ROCKII, and elastin. Fibronectin expression levels on the other hand were found to be decreased following HO-1 upregulation. The results of our study show that the hemin/HO-1 system regulates the tone and FEP of IAS. The hemin/HO-1 system thus provides a potential target for the development of new interventions aimed at treatment of gastrointestinal motility disorders, specifically the age-related IAS dysfunction.

A New Simplified Technique for Pediatric Anorectal Manometry

PEDIATRICS ◽  
1983 ◽  
Vol 71 (2) ◽  
pp. 240-245
Author(s):  
Allan J. Rosenberg ◽  
A. Richard Vela
Keyword(s):  
Anal Sphincter ◽  
Ganglion Cells ◽  
Internal Sphincter ◽  
False Negative ◽  
Rectal Biopsy ◽  
Rectal Balloon ◽  
Negative Results ◽  
Biopsy Specimens ◽  
Balloon Distension ◽  
False Negative Results

Using a new simple technique that is well tolerated and rapid for assessing anal sphincter functions in pediatric patients with fecal incontinence and constipation, 86 patients with varying degrees of anorectal dysfunction were tested. A microtip pressure transducer was used for recording anal sphincter responses to rectal balloon distension. Results were obtained within 15 to 30 minutes. In 17 patients, the internal anal sphincter showed no response or positive spike to balloon distension, consistent with the manometric diagnosis of aganglionic megacolon. These findings were confirmed by absence of ganglion cells on rectal biopsy. Sixty-nine children had normal internal sphincter relaxation to rectal distension. Ganglion cells were present in nine biopsy specimens. In the remaining 60 patients, no further workup of aganglionosis was necessary. There were no falsepositive or false-negative results. This technique has proved to be effective for initial evaluation of infants and children with constipation and encopresis.

Genesis of anal canal pressures in the opossum

1986 ◽  
Vol 251 (6) ◽  
pp. G765-G771 ◽  
Author(s):  
P. J. Culver ◽  
S. Rattan
Keyword(s):  
Anal Canal ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
External Anal Sphincter ◽  
Sphincter Pressure ◽  
Electromyographic Activity ◽  
Sphincter Muscle ◽  
Anal Sphincter Muscle ◽  
Adrenergic Antagonist ◽  
Alpha Chloralose

The purpose of the present investigation was to examine the role of the internal and external anal sphincters in the maintenance of resting pressures in the anal canal. The studies were performed in opossums anesthetized with alpha-chloralose. The radial and axial pressures in the anal canal were monitored using a continuously perfused catheter assembly. Electromyography of the external anal sphincter was monitored using bipolar tungsten hook electrodes. To examine the contribution of the external anal sphincter and surrounding skeletal muscle to the resting tone in the anal canal, pancuronium bromide was administered in a dose that abolished the electromyographic activity of the external anal sphincter muscle. The abolition of external anal sphincter activity did not modify the peak anal canal pressures, suggesting that these pressures are due to the internal anal sphincter. The alpha-adrenergic antagonist, phentolamine, did not modify the anal canal pressure, suggesting that basal internal anal sphincter pressure is not due to tonic adrenergic activity. Tetrodotoxin in a dose that produced obliteration of the anorectal reflex causing anal sphincter relaxation did not produce any change in the peak anal canal pressures. These studies show that the resting pressures in the anal canal of opossums are due to myogenic properties of the internal anal sphincter.

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