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Results for “Methacholine Compounds”

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At least 433 records · Page 24Linked to original sources

PubMed1978

Excitation of autonomic nerves by 4-aminopyridine in the isolated, blood-perfused sino-atrial node preparation of the dog.

4-Aminopyridine injected into the sinus node artery produced a long-lasting decrease in sinus rate preceded by a transient increase. With a large dose, a long-lasting increase in sinus rate was superimposed on the long-lasting decrease phase. The long-lasting decrease and increase in sinus rate were abolished by 1-hyoscyamine and propranolol respectively, and both were reduced by tetrodotoxin. These results can be interpreted as being due to excitation of autonomic nerves by 4-aminopyridine.

Animals↗

PubMed1978

The antiarrhythmic action of amitriptyline on arrhythmias associated with myocardial infarction in dogs.

The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conversion to normal sinus rhythm was evident. Amitriptyline administration resulted in conversion of the ventricular arrhythmia to a normal sinus rhythm in 100% of the animals tested at a mean dose of 1.3 +/- 0.1 mg/kg. Smaller doses also resulted in a dose-related decrease in non-sinus nodal pacemaker activity. Lidocaine, when administered to the same group of animals, produced a reduction of ectopic pacemaker activity, but did not eliminate it at a cumulative dose of 2 mg/kg. Antiarrhythmic doses of amitriptyline did not produce significant changes in arterial blood pressure, cardiac output or electrocardiographic parameters associated with atrioventricular or intraventricular conduction. The results of this study suggest that at very low doses amitriptyline may be an effective antiarrhythmic agent in ventricular arrhythmias associated with myocardial ischemia.

Amitriptyline↗

PubMed1980

Replacement of K+ with Rb+ or Cs+, and its effects on the mechanical responses to norepinephrine and methacholine in the rat vas deferens.

The rat vas deferens was stored overnight in cold, K+-free Krebs solution to deplete intracellular K+ then incubated in K+-, Rb+-, or Cs+-containing Krebs solution at 37 degrees C to load these ions inside the cells. After 4 h, the contents of K+ or Rb+ reached the level of K+ in the fresh vas deferens; the content of Cs+ was less than half that of the fresh vas deferens. Dose-response curves to norepinephrine and methacholine were determined under these conditions, and the curves in Rb+ or Cs+ solution were compared with those in K+ solution. The cold storage per se had little effect on the dose-response curves in K+ solution except that it slightly decreased the maximal response to norepinephrine. The dose-response curves in Rb+ solution were to the left of those in K+ solution. The maximal response to methacholine was greatly increased. On the other hand, the dose-response curves in Cs+ solution were to the right of those in K+ solution. The maximal responses were greatly decreased with both drugs. The results suggest that Rb+ but not Cs+ can fully substitute for K+ in the rat vas deferens response to norepinephrine and methacholine.

Animals↗

PubMed1982

Further support for the central origin of the gastric antisecretory properties of clonidine in conscious rats.

The effects of clonidine (CL) on interdigestive gastric acid secretion were studied in chronic gastric fistula rats and compared with those of St 91, a CL-like drug which does not cross the blood-brain barrier. CL induced a dose-dependent inhibition of gastric acid output when administered s.c. (ED50 13.5 micrograms X kg-1), in the lateral ventricle of the brain (ED50 5.80 micrograms X kg-1) or in the cisterna magna (ED50 0.49 micrograms X kg-1). St 91 and several alpha-adrenergic antagonists administered subcutaneously also inhibited gastric acid secretion dose dependently. Decreasing activities were prazosin greater than St 91 greater than phentolamine greater than yohimbine greater than piperoxan; phenoxybenzamine was a poor inhibitor. The anti-secretory properties of CL on basal secretion were antagonized by yohimbine and piperoxan. Other drugs either did not antagonize (phentolamine) or potentiated (phenoxybenzamine, prazosin) the CL effect, while yohimbine and phenoxybenzamine potentiated the response to St. 91. CL had no activity on methacholine while it drastically inhibited 2-DG-, histamine- and pentagastrin-stimulated gastric secretion. The inhibitory activity of CL on histamine stimulation was significantly decreased by yohimbine but not by phentolamine. These results confirm that the CL inhibition of the gastric acid secretion in unanesthetized rats is mediated at least partly through the stimulation of alpha 2-adrenergic receptors. Most of the data favour a major role of the CNS in the antisecretory activity of CL and suggest the possibility that most of the receptors involved are located in the medulla oblongata.

Adrenergic alpha-Antagonists↗

PubMed1983

Kinetics of antisecretory action of a new H2-antagonist, YM-11170, in conscious dogs.

The antisecretory property of YM-11170 was compared with that of cimetidine and atropine in the Heidenhain pouch dog. YM-11170 inhibited competitively dimaprit-induced gastric acid secretion in doses of 33 and 100 nmol/kg per h and its antisecretory potency was 148 times more pronounced than that of cimetidine. The secretory action of pentagastrin and methacholine was also inhibited by YM-11170 and cimetidine with doses similar to those required for the inhibition of dimaprit action although the inhibition by the H2-antagonists was not of the surmountable type. Atropine inhibited gastric secretion stimulated by methacholine and pentagastrin more strongly than that stimulated by dimaprit. It is concluded that YM-11170 is a competitive antagonist of dimaprit-induced gastric secretion in vivo and that the activity of the H2-antagonists in blocking gastric H2-receptors may reflect their inhibitory effect on the acid response to pentagastrin and methacholine.

Animals↗

PubMed1984

Differential relaxant effects of isoproterenol on methacholine- versus leukotriene D4-induced contraction in the guinea-pig trachea.

The ability of isoproterenol to relax guinea-pig trachea was examined in tissues precontracted with three concentrations of methacholine or three corresponding equieffective concentrations of leukotriene D4. Although increasing the concentration of either contractile agent progressively shifted isoproterenol concentration-response curves to the right, the shifts produced by methacholine were greater than those produced by leukotriene D4. Thus, the sensitivity of tracheal smooth muscle to beta-agonists depends upon the initial contractile state of the tissue, and the type of agent used to induce tone.

Airway Resistance↗

PubMed1984

Pharmacological characterization of the postjunctional beta-adrenoceptors in the rat gastric fundus.

In order to characterize the postjunctional beta-adrenoceptors in the rat gastric fundus, we studied the influence of beta-agonists and beta-antagonists on methacholine-contracted fundus strips. The mixed beta-agonist isopropylnoradrenaline and the beta 2-selective agonist fenoterol had a concentration-dependent relaxing effect and at higher concentrations completely inhibited the methacholine-induced tone. The reputedly beta 1-selective agonist prenalterol only produced about 50% inhibition and another reputedly beta 1-selective agonist, tazolol, had almost no relaxing effect. The beta-antagonists propranolol (beta 1 + beta 2), practolol (beta 1), H35/25 (beta 2) and ICI 118,551 (beta 2) all shifted the concentration-response curves for isopropylnoradrenaline and fenoterol in a parallel way to the right, but the slope of the Schild plot was not significantly different from 1 only for the antagonism of isopropylnoradrenaline by H35/25. The relaxing effect of prenalterol was only clearly antagonized by ICI 118,551. The results suggest that postjunctional beta 1- and beta 2-adrenoceptors are present in the rat gastric fundus.

Adrenergic beta-Agonists↗

PubMed1984

Cholinergic mechanism of acid secretion in the dog: an in vivo and in vitro comparison.

The effect of cholinergic stimulation on gastric acid secretion was examined in mongrel dogs using an in vivo and an in vitro preparation for comparison. The gastric fistula dog was used for the in vivo studies, and methacholine was infused directly into the artery supplying the fundus of the stomach to avoid systemic hemodynamic changes. Isolated parietal cells were used for the in vitro studies. In vivo, methacholine infused at 1 microgram/min was found to stimulate gastric acid secretion that was inhibited 98.5 +/- 1.4% by intravenously administered metiamide (H2 blocker) and 72 +/- 11% by intra-arterially administered glucagon. Glucagon had no effect on histamine stimulated acid secretion. In vitro, increasing concentrations of methacholine from 10(-7), 10(-6) to 10(-5) M stimulated [14C]aminopyrine uptake into parietal cells in a concentration dependent manner. This effect of methacholine was unaltered by 10(-4) M metiamide or 10(-6) M glucagon. However, atropine 10(-5) M totally blocked the stimulatory effect of methacholine. Our data suggest that the cholinergic mechanism of acid secretion is different when examined in vivo vs. in vitro even in the same species. In vivo histamine dependency has a major contribution to the cholinergic mechanism of acid secretion, whereas in vitro the interaction of the cholinergic agonist at the muscarinic receptor results in acid stimulation that does not require the presence of histamine.

Aminopyrine↗

PubMed1985

Modulation of cholinergic neurotransmission in canine airways by thromboxane mimetic U46619.

We studied the effect of a thromboxane A2-mimetic, U46619, on the contractile responses of canine bronchial smooth muscle to cholinergic stimulation in vitro. U46619 (3 X 10(-10) M), at a concentration that did not cause contraction, enhanced the effect of electrical field stimulation at all frequencies; histamine (10(-7) M) and prostaglandin F2 alpha (10(-7) M) did not. U46619 (3 X 10(-10) M) did not affect methacholine-induced contractions. U46619 may therefore increase the prejunctional release of acetylcholine.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1985

Muscarinic receptors in rat nasal mucosa are predominantly of the low affinity agonist type.

Specific [3H]l-quinuclidinyl benzilate binding to rat nasal mucosa homogenates occurs to a homogeneous class of binding sites with Kd = 60 +/- 2 10(-12) M and Bmax = 8.1 +/- 2 pmol/g tissue. Binding is stereoselectively inhibited by benzetimide enantiomers. Pirenzepine inhibits [3H]l-quinuclidinyl benzilate binding with low affinity (Ki = 5.0 10(-7) M), classifying the binding sites as muscarinic M2-receptors. Methylfurtrethonium and methacholine inhibit [3H]l-quinuclidinyl benzilate binding following an almost sigmoid curve at high concentrations pointing to the presence of mainly low affinity agonist binding sites.

Animals↗

PubMed1985

Polyamines and putreanine relax respiratory tract smooth muscle in the guinea-pig.

Spermidine, spermine, and putreanine, a metabolite of spermidine, caused transient relaxation of the isolated guinea-pig trachealis. The spermidine effect was not blocked by ouabain, propranolol or indomethacin. Spermidine treatment was shown to desensitize the tissue to subsequent additions of spermidine. After exposure to spermidine and repeated washes with spermidine-free solution, trachealis responded to KCl (30 mM) with a paradoxical relaxation. This relaxation was not blocked by propranolol, ouabain or indomethacin.

Amino Acids, Diamino↗

PubMed1985

Combined actions of bronchodilators in guinea-pigs depend on the severity of cholinergic airway obstruction.

The effects of theophylline (THEO), given alone and in combination with terbutaline (TER) or ipratropium bromide (IPRA), were investigated on the dose-related methacholine (MeCh)-induced bronchoconstriction in anaesthetized guinea-pigs. MeCh increased lung resistance (RL) relatively more than it decreased dynamic lung compliance (CDYN), which indicates obstruction of mainly large airways. THEO counteracted MeCh effects on CDYN more than those on RL, in comparison with the effects of TER or IPRA. Combined treatment with THEO + TER or THEO + IPRA usually antagonized the MeCh-induced rise in RL more than did the individual drugs, but the decrease in CDYN was not prevented more than by THEO alone. The actions of the bronchodilator combinations on RL depended on the degree of airway obstruction, being additive on mild or moderate states and synergistic on the most severe bronchoconstriction. Subtherapeutic doses of TER antagonized rather than enhanced the effects of THEO on RL. These results suggest that THEO has a more peripheral apparent site of action than TER or IPRA. A sufficient dose of a beta 2-agonist seems decisive in order to produce an enhanced bronchodilator effect with THEO on large airways.

Airway Obstruction↗

PubMed1985

Organ culture of young rat vas deferens as an in vitro model for the study of denervation supersensitivity.

To investigate whether organ culture is a suitable in vitro model for studying the mechanisms of denervation-induced supersensitivity, we cultured 1-week-old rat vas deferens for 3 days with a basic applied tension of 20 mg. Cultured muscles showed supersensitivity to norepinephrine and methacholine with concomitant elevation of the maximal response. To compare these changes with those caused by denervation, young rats were chemically denervated by injecting 6-hydroxydopamine, and consequent sensitivity changes were investigated. Denervated muscles showed non-specific supersensitivity to norepinephrine and methacholine but the maximal response did not increase. When these denervated muscles were organ-cultured, they showed no or only a slight increase in sensitivity to norepinephrine and methacholine, but the maximal response increased greatly. These observations led to the suggestion that the increase in sensitivity may be mediated through the same mechanisms as those for denervation supersensitivity. The elevation of the maximal response was suggested to be produced by the improvement of cell-to-cell conduction as well as some other unknown factor(s) probably specific to organ culture. Thus, it was concluded that organ-cultured 1-week-old rat vas deferens is a useful model to study the mechanisms of denervation supersensitivity.

Animals↗

PubMed1985

Age-related changes in the reactivity of the rat jejunum to cholinoceptor agonists.

The contractile effects of barium, potassium, acetylcholine and acetyl-beta-methylcholine were studied in jejunum of 4, 12 and 20 month-old rats. The effects of age on the sensitivity and responsiveness of the jejunum to the agonists were examined using cumulative dose administration and measuring the pD2. The maximum contraction produced by the agonists and the sensitivity to barium and potassium were not modified by aging. In the middle-aged animals, the jejunum sensitivity to acetylcholine decreased while the sensitivity to acetyl-beta-methylcholine was not statistically different from that of 4 month-old rats. Since at this age (12 months) the acetylcholinesterase activity increased, the reduction in the sensitivity to acetylcholine could have been due to the increase in the activity of the metabolizing enzyme. Otherwise, in the jejunum from the older animals the sensitivity for both cholinoceptor agonists, acetylcholine and acetyl-beta-methylcholine, increased 5-fold when compared with the middle-aged animals. However, compared with the jejunum of 4 month-old rats the sensitivity to acetylcholine, to 20 month-old animals, was not altered while the sensitivity to acetyl-beta-methylcholine was increased. At this age (20 months), the jejunum acetylcholinesterase activity was increased when compared with that of 4 month-old rats and was not modified when compared with that of 12 month-old rats. The change in supersensitivity to cholinoceptor agonists could not have been due to an alteration in muscarinic receptor affinity, since the pA2 for atropine was not modified with increasing age. These results suggest that after an increase in acetylcholinesterase activity around month 12, the jejunum develops an adaptative supersensitivity to cholinoceptor agonists.

Acetylcholine↗

PubMed1986

Human small airway smooth muscle responses in vitro; actions and interactions of methacholine, histamine and leukotriene C4.

The in vitro contractile responses to methacholine, histamine and leukotriene C4 (LTC4) were measured in human bronchiolar strips obtained after surgery. LTC4 was approximately 100 times more potent than both methacholine and histamine (mean pD2 values were 8.01, 6.18 and 5.87 respectively). All three agonists produced the same maximum contractile response (Tmax) and no difference was found in the time course of methacholine-, histamine- and LTC4-induced responses. When methacholine, histamine and LTC4 were applied in succession on one airway preparation, no interactions between these agonists were demonstrated for pD2. However, interactions were found concerning Tmax. The sensitivity (pD2) could be measured accurately and reproducibly and showed a relatively small within-patients variation (coefficients of variation 4-5%). In contrast, Tmax showed a considerable within-patients variation (coefficients of variation 47-91%), which limits its usefulness when small numbers of airway preparations are studied.

Airway Resistance↗

PubMed1986

Release of [Leu5]enkephalin immunoreactivity from the isolated perfused rat stomach.

The release of [Leu5]enkephalin immunoreactivity ([Leu5]enk-IR) from the isolated perfused rat stomach was demonstrated under basal conditions in the presence of peptidase inhibitors (0.1 microM thiorphan, 1 microM captopril and 2 microM bestatin). Depolarization with 50 mM KCl resulted in a four-fold increase in both [Leu5]enk-IR and gastrin (IR-gastrin) levels. Administration of the nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (10 microM) stimulated the release of [Leu5]enk-IR in a calcium-dependent manner. The muscarinic acetylcholine receptor agonist methacholine (10 microM) had no effect on [Leu5]enk-IR release.

Animals↗

PubMed1986

Altered endothelium-mediated relaxation after denervation of growing rabbit ear artery.

The relaxation response to methacholine and sodium nitroprusside was examined in ring segments from the posterior auricular artery and its continuation the central ear artery in growing rabbits 2, 4, 6 and 8 weeks following unilateral adrenergic and sensory denervation. The maximal relaxation achieved by methacholine (endothelium-dependent) was significantly depressed in the denervated arteries compared with the contralateral controls. Sodium nitroprusside (endothelium-independent relaxant agent) elicited the maximal relaxation in all tissues. These results demonstrated impaired arterial endothelium-dependent relaxation to methacholine after chronic denervation.

Animals↗

PubMed1986

Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle.

The influence of the epithelium on the reactivity of guinea-pig tracheal smooth muscle in vitro was investigated. Mechanical removal of the epithelium produced contrasting effects on methacholine-, histamine- and K+-induced contractions of tracheal strips. Epithelium removal resulted in 2.1-fold shifts to the left of histamine and methacholine concentration-response curves, and an increase in the maximum response to histamine; the maximum response to methacholine was unaffected. Epithelium removal had little effect on the sensitivity, but decreased the maximum response to K+. The results suggest that inhibitory and excitatory factor(s) are released from epithelial cells, and that these factors modulate the reactivity of the smooth muscle. Indomethacin (1 microM) produced in epithelium-containing preparations qualitatively identical effects on the sensitivity to methacholine and on the maximum response to histamine as removal of the epithelium. However, indomethacin was without effect on the sensitivity to histamine in the presence or absence of the epithelium. Alterations in the production or release of epithelial cell-derived factors may contribute to the airway hyperreactivity observed in respiratory disorders.

Airway Resistance↗