Tachykinins mediate noncholinergic excitatory neural responses in the circular muscle of rat proximal colon

1998 ◽  
Vol 76 (6) ◽  
pp. 684-689 ◽  
Author(s):  
R Serio ◽  
F Mulè ◽  
F Bonvissuto ◽  
A Postorino
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Circular Muscle ◽  
Proximal Colon ◽  
Rat Colon ◽  
Neurokinin A ◽  
Receptor Antagonists ◽  
Excitatory Junction Potential ◽  
Excitatory Responses ◽  
Junction Potential

Using the sucrose-gap technique, we attempted to assess a role for tachykinins (TKs) in mediating noncholinergic excitatory junction potential (EJP) and contraction, in the circular muscle of rat proximal colon. Excitatory responses were evoked by submaximal electrical field stimulation (EFS) in the presence of atropine (1 µM), guanethidine (1 µM), indomethacin (10 µM), and Nomega -nitro-L-arginine methyl ester (L-NAME) (100 µM). The NK1 receptor antagonist, SR 140,333 (up to 3 µM) or the NK2 receptor antagonists, SR 48,968 and MEN 10,627 (up to 5 µM) produced a partial inhibition of the excitatory responses to EFS. The co-administration of the selective NK1 and NK2 receptor antagonists produced additive effects on the responses to EFS. Selective NK1 receptor agonist, [Sar9, Met (O2)11]-substance P, induced depolarization and contraction, antagonized by SR 140,333, but not by NK2 receptor antagonists. NK2 receptor agonist, [ betaAla8]-neurokinin A (4-10), also produced electrical and mechanical excitatory effects that were antagonized by SR 48,968 or MEN 10,627, but not by the NK1 receptor antagonist. Our results provide evidence that, in circular muscle of rat colon, endogenous tachykinins are the main excitatory transmitters for nonadrenergic, noncholinergic (NANC) excitation and their action is mediated by both NK1 and NK2 receptors.Key words: NK1 receptor, NK2 receptor, nonadrenergic, noncholinergic (NANC) excitatory junction potential, intestine.

Noradrenergic, noncholinergic inhibitory junction potentials in rat proximal colon: role of nitric oxide

1995 ◽  
Vol 73 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Rosa Serio ◽  
Flavia Mulé ◽  
Alessandra Postorino
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Proximal Colon ◽  
No Synthase ◽  
Resting Potential ◽  
Rat Colon ◽  
Inhibitory Junction Potential ◽  
Junction Potential

Using a single sucrose gap apparatus, experiments were performed to determine the involvement of nitric oxide (NO) in the generation of noradrenergic, noncholinergic (NANC) inhibitory junction potentials in circular muscle of rat proximal colon. Inhibitors of NO synthase, Nω-nitro-L-arginine and its methyl ester, reduced the amplitude of the electrically evoked inhibitory junction potentials, without affecting membrane resting potential. Such an effect was stereospecific and it was prevented by L-arginine but not by D-arginine. Sodium nitroprusside induced a tetrodotoxin-resistant hyperpolarization, which was not affected by NO synthase inhibitors. Aparnin reduced sodium nitroprusside induced hyperpolarization, as well as NANC inhibitory junction potentials, and α-chymotrypsin decreased the amplitude of electrical field stimulation evoked responses. Residual responses after NO synthase inhibitors or after α-chymotrypsin were further reduced by pretreatment with α-chymotrypsin or NO synthase inhibitors, respectively. These results suggest that, in rat colonic circular muscle, NO plays an important role in NANC inhibitory junction potential generation. However, another mechanism, peptidergic in nature, is also involved.Key words: nonadrenergic noncholinergic nerves, inhibitory junction potential, nitric oxide, rat colon.

scholarly journals Adenosine A1receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart

1999 ◽  
Vol 276 (2) ◽  
pp. H341-H349 ◽  
Author(s):  
Gavin R. Norton ◽  
Angela J. Woodiwiss ◽  
Robert J. McGinn ◽  
Mojca Lorbar ◽  
Eugene S. Chung ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Ventricular Myocytes ◽  
Physiological Role ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Perfused Rat Hearts

Presently, the physiological significance of myocardial adenosine A2a receptor stimulation is unclear. In this study, the influence of adenosine A2a receptor activation on A1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat hearts and isolated rat ventricular myocytes. In isolated perfused hearts, the selective A2a receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10−8 M)-elicited contractile responses (+dP/d t max) in a dose-dependent manner. The effect of ZM-241385 on adenosine-induced antiadrenergic actions was abolished by the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10−7 M), but not the selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10−7 M). The A2a receptor agonist carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at 10−5 M attenuated the antiadrenergic effect of the selective A1 receptor agonist 2-chloro- N 6-cyclopentyladenosine (CCPA), whereas CSC did not influence the antiadrenergic action of this agonist. In isolated ventricular myocytes, CSC potentiated the inhibitory action of adenosine on Iso (2 × 10−7 M)-elicited increases in intracellular Ca2+concentration ([Ca2+]i) transients but did not influence Iso-induced changes in [Ca2+]itransients in the absence of exogenous adenosine. These results indicate that adenosine A2areceptor antagonists enhance A1-receptor-induced antiadrenergic responses and that A2a receptor agonists attenuate (albeit to a modest degree) the antiadrenergic actions of A1 receptor activation. In conclusion, the data in this study support the notion that an important physiological role of A2a receptors in the normal mammalian myocardium is to reduce A1 receptor-mediated antiadrenergic actions.

scholarly journals THE EFFECT OF HISTAMINE H1 RECEPTOR ANTAGONISTS ON THE MORPHINE-INDUCED ANTINOCICEPTION IN THE ACUTE TRIGEMINAL MODEL OF NOCICEPTION IN RATS

2016 ◽  
Vol 10 (1) ◽  
pp. 76 ◽  
Author(s):  
Emad Khalilzadeh ◽  
Farzin Azarpey ◽  
Reza Hazrati
Keyword(s):  
Receptor Antagonist ◽  
Intraperitoneal Injection ◽  
Receptor Agonist ◽  
Pain Response ◽  
Combined Treatments ◽  
H1 Receptor ◽  
Receptor Antagonists ◽  
Corneal Surface ◽  
Histamine H1 Receptor ◽  
Trigeminal Pain

ABSTRACTObjective: In this study, the effect of different classes of histamine H receptor antagonists (chlorpheniramine, cetirizine, and fexofenadine), µopioid receptor agonist (morphine), and opioid receptor antagonist (naloxone) in separate and combined treatments were investigated on the acutetrigeminal model of pain in rats.1Methods: Eye wiping test used for induction of acute trigeminal pain by putting a drop of NaCl, 5 M solution (40 µl) on the corneal surface of the eye,and the number of eye wipes counted during the first 30 seconds.Results: Intraperitoneal injection of both chlorpheniramine and cetirizine at doses of 10 and 20 mg/kg significantly inhibited the acute trigeminal pain.However, fexofenadine did not change corneal pain response. Morphine at doses of 1.25, 2.5, and 5 mg/kg reduced eye wipe responses. Administrationof both chlorpheniramine and cetirizine but not fexofenadine before morphine-enhanced morphine analgesic activity, also pretreatment of animalswith naloxone inhibited morphine, chlorpheniramine, and cetirizine-induced analgesia in the acute corneal pain.Conclusion: Our results showed that chlorpheniramine as a histamine H antagonist that efficiently Penetrates blood-brain barrier (BBB) andcetirizine with less penetration of BBB but not fexofenadine (an H11 receptor antagonist with a negligible brain-accessibility) could induce analgesiain the acute corneal pain via opioidergic mechanism. Coadministration of morphine with chlorpheniramine or cetirizine could enhance its analgesicactivity in the acute trigeminal model of pain in rats.Keywords: Trigeminal pain, Morphine, Histamine H1 receptor antagonists, Naloxone, Rats.

Different types of contractions in rat colon and their modulation by oxidative stress

2001 ◽  
Vol 280 (4) ◽  
pp. G546-G554 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna
Keyword(s):  
Potential Role ◽  
Contractile Response ◽  
Circular Muscle ◽  
Distal Colon ◽  
Proximal Colon ◽  
Rat Colon ◽  
Hla B27 ◽  
Different Types

The aim of this study was to investigate the modulation of in vitro rat colonic circular muscle contractions by dextran sodium sulfate (DSS)-induced inflammation and in spontaneous inflammation in HLA-B27 rats. We also examined the potential role of hydrogen peroxide (H2O2) in modulating excitation-contraction coupling. The muscle strips from the middle colon generated spontaneous phasic contractions and giant contractions (GCs), the proximal colon strips generated primarily phasic contractions, and the distal colon strips were mostly quiescent. The spontaneous phasic contractions and GCs were not affected by inflammation, but the response to ACh was suppressed in DSS-treated rats and in HLA-B27 rats. H2O2production was increased in the muscularis of the inflamed colon. Incubation of colonic muscle strips with H2O2suppressed the spontaneous phasic contractions and concentration and time dependently reduced the response to ACh; in the middle colon, it also increased the frequency of GCs. We conclude that H2O2mimics the suppression of the contractile response to ACh in inflammation. H2O2also selectively suppresses phasic contractions and increases the frequency of GCs, as found previously in inflamed dog and human colons.

Action of alpha 2A-adrenergic receptors in circular smooth muscle of canine proximal colon

1992 ◽  
Vol 262 (3) ◽  
pp. G517-G524 ◽  
Author(s):  
L. Zhang ◽  
K. D. Keef ◽  
M. E. Bradley ◽  
I. L. Buxton
Keyword(s):  
Smooth Muscle ◽  
Adenylate Cyclase ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Agonist ◽  
Circular Muscle ◽  
Proximal Colon ◽  
Affinity Binding ◽  
Circular Smooth Muscle

Addition of the alpha 2-adrenergic receptor agonist clonidine (1 microM) to tetrodotoxin-treated strips of canine colonic circular smooth muscle resulted in a significant increase in contractile force that was blocked by addition of the alpha 2-antagonist yohimbine (0.1 microM). The alpha 2-receptor antagonist radioligand [3H]rauwolsine bound rapidly and reversibly to a single class of saturable sites (Bmax, 38.4 +/- 6.2 fmol/mg protein) in colonic circular smooth muscle membranes with an affinity (KD = 5.1 +/- 0.9 nM) characteristic of alpha 2-adrenergic receptors in smooth muscle. Studies in cells freshly isolated from circular muscle of canine proximal colon verified the smooth muscle origin of these receptors. Rank order of potency of alpha 2-adrenergic receptor antagonists in competition for [3H]rauwolsine binding was yohimbine greater than oxymetazoline much greater than prazosin. Affinity of alpha 2-receptors for yohimbine was indistinguishable from that of its optical isomer, rauwolsine, in both competition studies (KI = 3.4 nM) and in saturation-binding experiments employing [3H]yohimbine directly (KD = 4.2 nM). The alpha-receptor agonist epinephrine, in competition studies employing [3H]rauwolsine, revealed high-affinity binding sites that were converted to low-affinity binding sites for agonist by addition of 100 microM GTP gamma S. Addition of the alpha 2 more-selective agonist clonidine (100 microM) resulted in inhibition of adenylate cyclase activity that was abolished by pretreatment of tissue strips with pertussis toxin suggesting coupling of the alpha 2-receptor in colon to adenylate cyclase via the GTP-binding protein Gi. Our data demonstrate a physiological role for adenylate cyclase-coupled receptors of the alpha 2A-subtype in canine colon circular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP is a mediator of the fast inhibitory junction potential in human jejunal circular smooth muscle

1999 ◽  
Vol 276 (6) ◽  
pp. G1373-G1379 ◽  
Author(s):  
L. Xue ◽  
G. Farrugia ◽  
M. G. Sarr ◽  
J. H. Szurszewski
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Time Course ◽  
Purinergic Receptors ◽  
Fast Component ◽  
Circular Smooth Muscle ◽  
Inhibitory Junction Potential ◽  
Junction Potential

The neurotransmitter(s) that generates the fast component of the inhibitory junction potential (IJP-F) in human jejunal circular smooth muscle is not known. The aim of this study was to determine the role of ATP and purinergic receptors in the generation of the IJP-F in human jejunal circular smooth muscle strips. The P2-receptor antagonist suramin (100 μM) reduced the IJP-F by 28%. Apamin (1 μM) reduced the IJP-F by 25%. Desensitization of muscle strips with the putative P2x-receptor agonist α,β-methylene ATP (α,β-MeATP, 100 μM) decreased the IJP-F by 44%, and desensitization with the putative P2y-receptor agonist adenosine 5′- O-2-thiodiphosphate (ADPβS) completely abolished the IJP-F. Desensitization with the putative P2y-receptor agonist 2-methylthioATP had no effect on the IJP-F. Exogenous ATP evoked a hyperpolarization with a time course that matched the IJP-F. The ATP-evoked hyperpolarization was reduced by apamin and suramin, reduced by desensitization with α,β-MeATP (69% decrease), and abolished by desensitization with ADPβS. These data suggest that the IJP-F in human jejunal circular smooth muscle is mediated in part by ATP through an ADPβS-sensitive P2receptor.

Turning behavior induced in mice by a neurokinin A receptor agonist: Stereoselective blockade by SR 48968, a non-peptide receptor antagonist

1993 ◽  
Vol 149 (1) ◽  
pp. 40-42 ◽  
Author(s):  
Martine Poncelet ◽  
Christiane Gueudet ◽  
Xavier Emonds-Alt ◽  
Jean-Claude Brelière ◽  
Gérard Le Fur ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Neurokinin A ◽  
Turning Behavior ◽  
Peptide Receptor

Effects of serotonergic agonists and antagonists on ganglion cells in the goldfish retina

1992 ◽  
Vol 9 (3-4) ◽  
pp. 353-364 ◽  
Author(s):  
Steven H. Hensley ◽  
Joel L. Cohen
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Ganglion Cells ◽  
Dopamine Receptor Antagonist ◽  
Extracellular Recordings ◽  
Different Types ◽  
Teleost Retina ◽  
Excitatory Responses ◽  
On And Off Pathways ◽  
Goldfish Retina

AbstractExtracellular recordings were made from the isolated goldfish retina during superfusion with various serotonergic agonists and antagonists to determine the effects of these drugs on the maintained activity and response properties of the ganglion cells. Superfusion of the retina with serotonin (25–500 μM) increased the maintained activity of OFF-center ganglion cells and decreased the maintained activity of ON-center ganglion cells. In addition, serotonin also attenuated the excitatory responses to annular stimuli, suggesting a decrease in the strength of surround input to the ganglion cells. The effects of serotonin on OFF-center ganglion cells were mimicked by the nonselective 5-HT1, agonist 5-MeOT and the 5-HT1 receptor agonist 8-OH-DPAT, while only 5-MeOT mimicked the action of serotonin on ON-center ganglion cells. The effects of exogenously applied serotonin on the ganglion cells could be blocked by the mixed 5-HT1/5-HT2 receptor antagonist methysergide but not by the 5-HT2 receptor antagonist mianserin or the dopamine receptor antagonist haloperidol.These results support previous anatomical and biochemical evidence that serotonin functions in a neurotransmitter or neuromodulatory role in the teleost retina and suggest that serotonin may be involved in modulating the maintained activity and surround input to the ganglion cells. The results also indicate that two different types of receptors may mediate the actions of serotonin in the ON and OFF pathways, respectively.

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