Home About us Contact
|
Home About us Contact | ||
|
|
||
Guinea-pig Ileum (guinea-pig + ileum)
Selected AbstractsEstimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological methodACTA PHYSIOLOGICA, Issue 2 2010K. F. Nilsson Abstract Aim:, Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations. Methods:, Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p -sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC. Results:, Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10,6 m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%). Conclusion:, Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose,response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems. [source] Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channelsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2008Anwarul Hassan Gilani Abstract This study describes the spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory and urinary bladder relaxant properties of Hyoscyamus niger to rationalize some of its medicinal uses. The crude extract of H. niger seeds (Hn.Cr) caused a complete concentration-dependent relaxation of spontaneous contractions of rabbit jejunum, similar to that caused by verapamil, whereas atropine produced partial inhibition. Hn.Cr inhibited contractions induced by carbachol (1 ,m) and K+ (80 mm) in a pattern similar to that of dicyclomine, but different from verapamil and atropine. Hn.Cr shifted the Ca2+ concentration,response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca2+ channel-blocking mechanism in addition to an anticholinergic effect. In the guinea-pig ileum, Hn.Cr produced a rightward parallel shift of the acetylcholine curves, followed by a non-parallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine. Hn.Cr exhibited antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation in mice. In guinea-pig trachea and rabbit urinary bladder tissues, Hn.Cr caused relaxation of carbachol (1 ,m) and K+ (80 mm) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca2+ antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect. A constituent, ,-sitosterol exhibited Ca2+ channel-blocking action. These results suggest that the antispasmodic effect of H. niger is mediated through a combination of anticholinergic and Ca2+ antagonist mechanisms. The relaxant effects of Hn.Cr occur at much lower concentrations in the trachea and bladder. This study offers explanations for the medicinal use of H. niger in treating gastrointestinal and respiratory disorders and bladder hyperactivity. [source] Synthesis and biological activity of homoarginine-containing opioid peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 1 2007Jan Izdebski Abstract Two tris-alkoxycarbonyl homoarginine derivatives, Boc-Har{,,,,-[Z(2Br)]2}-OH and Boc-Har{,,,,-[Z(2Cl)]2}-OH, were prepared by guanidinylation of Boc-Lys-OH, and used for the synthesis of neo-endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc-Lys(Fmoc)-OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide-resin was guanidinylated with N,N,-[Z(2Br)]2 - or N,N,-[Z(2Cl)]2 - S -methylisourea. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin-like enzymes. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Medicinal plants in Suriname: hypotensive effect of Gossypium barbadenseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2004J. A. Hasrat ABSTRACT In traditional medicine Gossypium barbadense L. is used against hypertension. Looking for a scientific basis for this use, the blood-pressure-lowering effect of the decoction of the leaves was confirmed. Fraction II (frII) of the crude extract of G. barbadense showed a dose-dependent hypotensive effect in anaesthetized rats. In hexamethonium-treated rats, the blood-pressure-lowering effect of frII was almost abolished. A small decrease of the blood-pressure-lowering effect was followed by an increase in the blood pressure. Phentolamine antagonized the increase in blood pressure in hexamethoniumtreated rats. High doses of atropine (4 mg/rat) suppressed both depressor and heart effects. In-vitro experiments revealed that atropine did not antagonize the contraction of the ileum of the rat. Tripelennamine in a concentration of 100 ,g could not influence the contraction either, whereas 300 ,g did. In the guinea-pig ileum 10 ,g tripelennamine did not reduce the contraction significantly. In the mechanism of action of frII, acetylcholine receptors could be involved, but not histaminergic or adrenergic receptors. Although it is still not known which compound(s) in G. barbadense is (are) the active substance(s), the results obtained may explain the use of this plant in traditional medicine in Suriname. [source] Propagating contractions of the circular muscle evoked by slow stretch in flat sheets of guinea-pig ileumNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2001S. J. H. Brookes Flat sheet preparations of guinea-pig ileum were stretched circumferentially and the propagation of circular muscle contractions along the preparation was investigated. Slow stretch, at 100 ,m s,1, of a 50-mm long flat sheet of intestine, evoked circular muscle contraction orally, which propagated, without decrement, for up to 30 mm. This occurred despite circular muscle shortening being prevented, and in the absence of propulsion of contents. Thus, propagation in this flat sheet preparation could not explained on the basis of neuro-mechanical interactions, as previously proposed. Irrespective of the length of preparations, contraction amplitude decreased significantly in the most aboral 10,15 mm of intestine. This was not due to descending inhibitory pathways, but was associated with interruption of ascending excitatory pathways near the aboral end. Slow waves were not detected in circular muscle cells in any preparation (n=8). Smooth muscle action potentials evoked in circular muscle cells, in the presence of tetrodotoxin (TTX, 0.6 ,mol L,1), did not propagate for more than 1 mm in the longitudinal axis. Propagation of circular muscle activity, evoked by slow stretch of flat sheet preparations, reveals the presence of a mechanism other than myogenic spread or the neuro-mechanical interactions previously proposed to account for propagation; the nature of this mechanism remains to be determined. [source] Pharmacological studies on siculine syrup.PHYTOTHERAPY RESEARCH, Issue 2 2009II: effects on smooth, cardiovascular muscle preparations, skeletal Abstract Earlier pharmacological screening showed that siculine syrup (a traditional herbal remedy purported to be useful in the prevention and treatment of sickle cell pain , crises, due to sickle cell anaemia , SCA) had antisickling and analgesic activities as well as antimicrobial and diuretic effects. SCA is an important haemoglobinopathy in Africa and many other communities/countries worldwide, with relatively high morbidity and mortality. The present study was to determine the effects of the extract on various isolated muscle preparations , smooth, skeletal and cardiovascular. Siculine (4,20 µg/mL), like acetylcholine (40,400 µg/mL), contracted the isolated rat uterus concentration dependently. Similar effects were observed with the guinea-pig ileum and rabbit jejunum (2,20 µg/mL). In contrast to these effects, the direct (muscle) and indirect (nerve) stimulations of rat phrenic nerve,diaphragm were relaxed by siculine (4 and 8 µg/mL) and d -tubocurarine (0.8 µg/mL). Siculine also concentration-dependently decreased both the rate and force of contraction of guinea-pig atria and rabbit heart and also resulted in a fall in cat blood pressure in a manner similar to those of acetylcholine. The possible therapeutic and/or toxicological consequences of these effects including the hypotensive activity is noteworthy since siculine syrup is used by the local population for the prevention and treatment of sickle cell pain crises. Copyright © 2008 John Wiley & Sons, Ltd. [source] Antispasmodic activity of extracts and compounds of Acalypha phleoides Cav.,PHYTOTHERAPY RESEARCH, Issue 2 2004Adela Astudillo Abstract The aerial parts of Acalypha phleoides are usually prescribed in the Mexican traditional medicine for a variety of gastrointestinal complaints. The MeOH,CHCl3 (1:1) extract of the aerial part of A. phleoides showed an inhibitory effect on the gastrointestinal propulsion of a charcoal meal in mice. In isolated guinea-pig ileum, this extract produced a concentration dependent inhibition of the contractions induced by 5-hydroxytryptamine, but it was unable to inhibit the contractions elicited by acetylcholine, histamine, KCl and BaCl2. This extract produced also a concentration dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum. This inhibitory activity was partially blocked by propranolol. The essential oil, obtained from the aerial part of this plant, was more potent than the MeOH,CHCl3 (1:1) extract in inhibiting the spontan-eous pendular movement of the rabbit jejunum. Thymol, camphor and , -terpinene were identi,ed from the essential oil by GC-MS. These monoterpenes showed antispasmodic activity in the rabbit jejunum preparation, thymol was the most active compound, followed by camphor and , -terpinene. Thymol and camphor in high concentrations also showed tracheal relaxant properties, but , -terpinene did not. These in vivo and in vitro results tend to support the traditional use of A. phleoides as an antispasmodic agent. Copyright © 2004 John Wiley & Sons, Ltd. [source] Functional antagonism between nitric oxide and ATP in the motor responses of guinea-pig ileumAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2000Chr. Ivancheva 1 The interaction of nitric oxide and ATP in the non-adrenergic, non-cholinergic (NANC) motor responses and the presence of NADPH-diaphorase and quinacrine-positive myenteric neurones were studied on guinea-pig ileum using mechanographic, histochemical and quinacrine-fluorescence techniques. In the presence of phentolamine, propranolol and atropine, the non-precontracted longitudinally oriented organ bath preparations responded to sodium nitroprusside (1,100 ,m) or ATP (5,50 ,m) with tetrodotoxin (0.1 ,m)-resistant relaxation or contraction, respectively. The effects of ATP were suramin (50 ,m)- and apamin (5 ,m)-sensitive. 2 The NANC motor responses elicited by electrical stimulation (0.8 ms, 1,20 Hz, 20 s) consisted of tetrodotoxin-sensitive relaxation phase followed by a phase of twitch-like and tonic contractions. 3 NG-nitro-L-arginine (L-NNA, 0.1,0.5 mm) inhibited or abolished the relaxation phase. L-arginine (0.5 mm), but not D-arginine (0.5 mm), restored the relaxation phase in L-NNA-pretreated preparations. The relaxation phase increased after ATP-induced desensitization of purinoceptors and in the presence of suramin (50 ,m) but was abolished by apamin (5 ,m). 4 The phase of contractions was enhanced by L-NNA (0.1,0.5 mm) and restored by L-arginine (0.5 mm). The twitch-like and tonic contractions were decreased during ATP-induced purinoceptor desensitization and in the presence of suramin (50 ,m). Apamin (5 ,m) inhibited the tonic contractions. 5 The desensitization of purinoceptors by ATP did not change the L-NNA-induced inhibition of the relaxation phase but decreased the L-NNA-increased phase of contractions. L-NNA reduced the relaxation phase and increased the phase of contractions during purinoceptor desensitization. 6 We conclude that in the longitudinal muscle layer of the guinea-pig ileum, nitric oxide mediates the relaxation phase while ATP contributes via smooth muscle P2 purinoceptors to the phase of contractions suggesting a postjunctional functional antagonism between nitric oxide and ATP. The presence of NADPH-diaphorase- and quinacrine-positive neuronal cells and processes running to the muscle cells confirms a physiological role of nitric oxide and ATP in the ileal neurotransmission. [source] Pharmacological and functional characterization of the guinea-pig B2 bradykinin receptor stably expressed in CHO-K1 cell lineBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2002C Robert In the present study, pharmacological properties of a bradykinin B2 receptor amplified either from guinea-pig ileum or lung and homologous to the previously reported sequence except two amino-acid changes L124,P and N227,Y in the receptor protein were characterized. Tritiated bradykinin ([3H]-BK) specifically bound to the cloned guinea-pig B2 bradykinin receptor stably expressed in Chinese hamster ovary cells (CHO-K1) with a KD value of 0.29±0.07 nM. In competition experiments, bradykinin (BK) affinity constant value was 0.21±0.05 nM while the two specific kinin B1 ligands, des-Arg9 -bradykinin (DBK) and des-Arg9 -Leu8 -bradykinin (DLBK) were unable to compete with [3H]-BK. As the specific peptide antagonist D -Arg-[Hyp3,Thi5,D -Tic7,Oic8]-bradykinin (HOE140), (E)-3-(6-acetamido-3-pyridil)-N-[-N-[2,4-dichloro-3-[(2-methyl-8-quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657) and 1-[[3-[2,4-dimethylquinolin-8-yl)oxymethyl] - 2,4 - dichloro - phenyl]sulfonyl] - 2(S) - [[4-[4-(aminoiminomethyl)-phenylcarbonyl]piperazin-1-yl]carbonyl]pyrrolidine (LF16-0335C) exhibited a high affinity for this receptor with Ki values of 7.34±2.45 nM and 8.54±1.55 nM respectively. BK and kallidin (KD) increased inositol phosphates (IPs) levels with EC50 values of 0.44±0.12 nM and 6.88±0.28 nM, respectively. Neither DLBK nor DBK (0.01 nM to 10 ,M) stimulated or inhibited IPs turnover and as expected HOE140 did not raise IPs production. HOE140 (0.1 ,M) and LF 16-0335c (1 ,M) right shifted the BK response curve with pKB values of 9.2±0.4 and 8.4±0.3, respectively. The results indicate that this cloned guinea-pig receptor displayed typical pharmacological properties of a bradykinin B2 receptor and support the existence of a single B2 receptor in this species. British Journal of Pharmacology (2002) 135, 462,468; doi:10.1038/sj.bjp.0704494 [source] | ||||||||||