Rat Anococcygeus Muscle Research Articles

Neuronal Voltage Gated Potassium Channels May Modulate Nitric Oxide Synthesis in Corpus Cavernosum.

Potassium channels (K+Ch) in corpus cavernosum play an important role in the regulation of erection. Nitric oxide (NO) acts through opening of K+Ch leading to hyperpolarization and relaxation.Aim : This study aims to update knowledge about the role of voltage-gated K+Ch (KV) channels in erectile machinery and investigate their role in the control of NO action &/or synthesis in the corpus cavernosum.Methods : Tension studies using isolated rabbit corpus cavernosum (CC) strips and rat anococcygeus muscle were conducted. Results are expressed as mean ± SEM.Results : Electric field stimulation (EFS, 2–16 Hz) evoked frequency-dependent relaxations of the PE (phenylephrine)-precontracted CC strips. At 2 Hz, EFS-induced relaxation amounted to 73.17 ± 2.55% in presence 4-AP (10−3 M) compared to 41.98 ± 1.45% as control. None of the other selective K+Ch blockers tested inhibited EFS-induced relaxation. 4-AP (10−3M) significantly attenuated ACh-induced relaxation of rabbit CC where dose-response curve was clearly shifted upward, and attenuated SNP- induced relaxation, for example, to 49.28 ± 4.52% compared to 65.53 ± 3.01% as control at 10−6 M SNP. The potentiatory effect of 4-AP on EFS was abolished or reversed in presence of NG-nitro-L-arginine (L-NNA, non-selective nitric oxide synthase inhibitor, 10−5M, and 2 × 10−4M). Same results were observed in rat anococcygeus muscle which is a part of the erectile machinery in rats.Conclusion : This study provides evidence for the presence of prejunctional voltage-gated K+Ch in CC, the blockade of which may increase the neuronal synthesis of NO.

The effect of coniine on presynaptic nicotinic receptors.

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Effect of biliary cirrhosis on neurogenic relaxation of rat gastric fundus and anococcygeus muscle: role of nitric oxide pathway.

Cirrhosis, associated with a host of hemodynamic abnormalities, could affect the gastrointestinal (GI) tract motility. On the other hand, the nonadrenergic noncholinergic (NANC) neurotransmission has been shown to play a pivotal role in GI tract motility and has been linked with release of nitric oxide (NO) on electrical stimulation. In this study, we investigated the effect of biliary cirrhosis on the neurogenic relaxation of rat gastric fundus and anococcygeus muscle and also the possible role of nitric oxide system in this manner. Isolated gastric fundus and anococcygeus strips of sham-operated and biliary cirrhotic (4weeks after bile duct ligation) rats were mounted under tension in a standard organ bath. Electrical stimulation was applied to obtain NANC-mediated relaxations in precontracted gastric fundus and anococcygeus muscle. The neurogenic relaxations were examined in the presence of different doses of NO synthase inhibitor, N (w)-Nitro-L-Arginine Methyl Ester (L-NAME). The concentration-dependent relaxant responses to the NO donor sodium nitroprusside were also evaluated. The neurogenic relaxation of both gastric fundus and anococcygeus muscle was significantly (P<0.001) increased in cirrhotic animals. L-NAME (0.03-1,000µM) inhibited relaxations in both groups in a dose-dependent manner (P<0.001), but cirrhotic groups were more resistant to the inhibitory effects of L-NAME (P<0.01). Sodium nitroprusside-mediated relaxations were similar in two groups. This study for the first time demonstrated that cirrhosis increases the NO-mediated neurogenic relaxation of both rat gastric fundus and anococcygeus muscle, suggesting a crucial role for the neurogenic NO in the pathophysiology of disturbed GI motility in cirrhosis.

Effect of resveratrol on the erectile machinery is due to the underlying mechanisms of the alpha 1‐adrenoceptor activation (1097.2)

The anococcygeus muscle is part of the erectile machinery in male rodents whose innervation is mainly due the autonomic system. Activation of alpha1‐adreneceptor triggers the production of reactive oxygen species (ROS). Resveratrol (RESV) is an antioxidant compound. Hypothesis: RESV may reduce the contractile responses stimulated by alpha‐1‐adrenergic agonist, phenylephrine (PE). It was evaluated the effect of RESV on the contractile response to PE on the rat anococcygeus muscle. Male Wistar rats (n=5‐7) were killed by cervical dislocation (Ethics Committee Approval: 019/2012), the anococcygeus muscle was isolated and suspended in an organ chamber bath to measure isometric contractions. Preparations were stimulated with PE (1 nmol/L to 100 mmol/L) before and after 20 min incubation with RESV or RESV plus different drugs: prazosin (Pz: 10‐8 mol/L); 2‐APB (10‐4 mol/L); GF109203X (0.5x10‐5mol/L) or atorvastatin (ATV: 10‐4mol/L). Analysis: Student paired t‐test or one‐way ANOVA, Newman‐Keuls post‐test. RESV (10‐4 mol/L) reduced maximum contraction (MC) stimulated with PE (to 69.3±1.1%). Pz (alpha1‐adrenoceptor antagonist) + RESV reduced this MC (to 55.8±4.7%, p&lt;0.0001). 2‐APB (IP3 receptor antagonist) was effective on reducing MC (to 28.8±1.19, p&lt;0,001). RESV+2‐APB also reduced ME (to 5.3±1.4%, p&lt;0.0001). pD2 values were reduced under RESV+2‐APB incubation. Incubation with GF109203X (PKC inhibitor) was effective on reducing MC (to 40.5±7.3%, p&lt;0.0001). pD2 values were also altered after GF109203X incubation. ATV (NADPH oxidase inhibitor) +RESV reduced MC (56.9±7.7%, p&lt;0.0001). The signaling triggered through stimulation of PE on the alpha 1‐adrenoceptors are involved in the production of free radicals, which were sensitive to RESV.Grant Funding Source: Supported by CNPq/PIBIC, UNAERP

Structural limits on force production and shortening of smooth muscle

This study determined the factors that limit force production and shortening in two smooth muscles having very different relationships between active and passive force as a function of muscle length. The rat anococcygeus muscle develops active force over the range of lengths 0.2-2.0× the optimum length for force production (Lo). Passive tension due to extension of the resting muscle occurs only at lengths exceeding Lo. In contrast, the rabbit taenia coli develops force in the range of lengths 0.4-1.1 Lo, and passive force which is detectable at 0.56 Lo, increases to ~0.45 maximum active force at Lo, and increases sharply with further extension. The anococcygeus muscle can shorten to 0.2 Lo and the taenia coli to 0.4 Lo. Dynamic stiffness and energy usage at short muscle lengths suggest that the limit of shortening in the taenia coli, in contrast to the anococcygeus muscle, is not due to a failure of cross bridge interaction. Phosphorylation of the regulatory myosin light chains in intact muscles decreased to a small extent at short lengths compared to the decrease in force production. The differences in force production and the extent of shortening in the two muscles was maintained even when, following permeabilization, the myosin light chains were irreversibly phosphorylated with ATPγS, indicating that differences in activation played little, if any role. Ultrastructural studies on resting and activated muscles show that the taenia coli, which is rich in connective tissue (unlike the anococcygeus muscle) undergoes marked cellular twisting and contractile filament misalignment at short lengths with compression of the extracellular matrix. As a result, force is not transmitted in the longitudinal axis of the muscle, but is dissipated against an internal load provided by the compressed extracellular matrix. These observations on two very different normal smooth muscles reveal how differences in the relative contribution of active and passive structural elements determine their mechanical behavior, and how this is potentially modified by remodeling that occurs in disease and in response to changes in functional demand.

Antinicotinic activity of some 2-aminotetralin derivatives. A structure-activity relationship study.

The antagonistic potencies of some methoxy-2-aminotetralin derivatives on nicotinic type acetylcholine receptors were compared in rat anococcygeus muscle and frog rectus abdominis muscle preparations. Stimulation of intrinsic non-adrenergic non-cholinergic (NANC) nerves with nicotine (100 mumol/l) produced a 65.7 +/- 3.2% relaxation in phenylephrine (1 mumol/l) precontracted (2.53 +/- 0.20 g) preparations (n = 17). 2-Aminotetralin derivatives inhibited the nicotine-induced relaxations in rat anococcygeus muscle in a concentration-dependent manner with the following order of potency: BDI-60 > BDI-85 > BDI-51. Preincubation of frog rectus abdominis muscles with the test compounds caused noncompetitive antagonism as reflected by significant reductions in the maximum contractions obtained with nicotine. The order of potency according to their pD2' values was BDI-60 > BDI-85 > BDI-51. All three compounds possess antagonistic action with the same order of potency on both neuronal and muscular type nicotinic acetylcholine receptors. It has been concluded that doubling the n-propyl residue on the 2-amino moiety causes an increase in the antagonistic potency on nicotonic type acetylcholine receptors, while shifting of the 8-methoxy residue to the fifth position reduces it.

Synthesis and alpha 1-adrenoceptor antagonistic activity of some 4-amino-5,7-dimethyl-2-(substituted) aminopyrido (2,3-d) pyrimidines.

A series of new 4-amino-5,7-dimethyl-2- (substituted)aminopyrido(2,3-d)pyrimidines (5) have been synthesized and tested for selective alpha 1-adrenoreceptor antagonistic activity. Some of the compounds were found to antagonize alpha 1-adrenoreceptor in a competitive and reversible manner. When screened on rat anococcygeus muscle some of the compounds exhibited significant alpha 1-adrenoreceptor antagonistic activity (pA2 values in the range of 5.2-7.8). The most potent compound (5j) was evaluated by an in vivo method and was found to reduce the systolic and diastolic blood pressure of spontaneously hypertensive rats. The percentage reduction in blood pressure by test compound 5j was found to be higher than that of the standard drug prazosin (CAS 19216-56-9) at the same dose level (1 mg/kg p.o.). Chemically, prazosin is a 4-aminoquinazolin derivative. Pyridopyrimidine is a known bioisostere of quinazoline. The study revealed that isosteric replacement of the benzene ring of prazosin by a pyridine ring increases the potency.

Inhibition of sympathetic neurotransmission in the rat anococcygeus muscle by diazepam.

In the rat anococcygeus muscle, diazepam (1.8 X 10(-6) - 2.8 X 10(-5) M), dipyridamole (2 X 10(-6) - 3.2 X 10(-5) M) and ATP (2 X 10(-4) - 6.4 X 10(-3) M) concentration-dependently inhibited the motor response to field stimulation. Glycine (up to 7.5 X 10(-3) M) and GABA (up to 10(-4) M) had no effect on field stimulation. Concentrations of diazepam and dipyridamole which reduced motor response to field stimulation did not relax the tonically contracted rat anococcygeus muscle. However, at these concentrations, diazepam and dipyridamole potentiated the inhibitory responses of the tonically contracted rat anococcygeus muscle to ATP and field stimulation. It is suggested that diazepam and dipyridamole reduced the motor response to field stimulation by potentiating the inhibitory transmitter released during nerve stimulation. Also, since the time-course of the effect of diazepam and dipyridamole on the inhibitory responses to ATP and field stimulation are closely similar, the results would tend to provide additional support for the concept of purinergic transmission in the rat anococcygeus muscle.

Effects of pyroxamidine and guanethidine on contractile responses to field stimulation and to noradrenaline in the anococcygeus muscle and vas deferens of the rat

Abstract The effects of pyroxamidine (EMD 21192) and guanethidine on contractile responses were studied in the anococcygeus muscle and vas deferens of the rat. Pyroxamidine (10−6 and 10−5 M) and guanethidine (6 times 10−6 and 10−5 M) potentiated the responses to low concentrations of acetylcholine in the rat anococcygeus muscle. Following incubation of the muscle with 6-hydroxydopamine (10−3M for 3 h), pyroxamidine (10−5 M) and guanethidine (10−5 M) had no effect on responses to acetylcholine. This suggests that the potentiating effect of pyroxamidine and guanethidine on responses to acetylcholine is due to the release of subthreshold concentrations of noradrenaline. In the anococcygeus, pyroxamidine (10−6 and 10−5 M) and guanethidine (10−6 and 10−5 M) inhibited responses to field stimulation and potentiated responses to exogenously applied (−)-noradrenaline. The responses to field stimulation in the vas deferens were also inhibited by 10−5M pyroxamidine and by 10−5 M guanethidine. 10−6 M guanethidine, but not 10−5 M pyroxamidine, potentiated responses to (−)-noradrenaline in the vas deferens. In the presence of nortriptyline (10−6 M), a potent inhibitor of neuronal uptake, the inhibitory effects of pyroxamidine and guanethidine on responses to field stimulation were reduced or reversed and these drugs had no effect on responses to (−)-noradrenaline. This suggests that pyroxamidine is a noradrenergic neuron blocker and that its action is dependent on continued neuronal uptake. Following 6-hydroxydopamine incubation, 10−5 M pyroxamidine and 10−5 M guanethidine inhibited the responses to (−)-noradrenaline in the rat anococcygeus muscle. Thus it seems likely, at high concentrations, that these compounds have postsynaptic blocking activity.

Effect of atropine on the rat anococcygeus muscle.

Journal Article Effect of atropine on the rat anococcygeus muscle Get access Fola M Tayo Fola M Tayo Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 34, Issue 3, March 1982, Pages 202–203, https://doi.org/10.1111/j.2042-7158.1982.tb04225.x Published: 12 April 2011 Article history Received: 22 July 1981 Published: 12 April 2011

Evidence for a Postsynaptic Action of Neostigmine on Muscarinic Receptors in the Anococcygeus Muscle of the Rat

In the rat anococcygeus muscle neostigmine induces atropine-sensitive, significant leftward displacements of the log concentration-response curves to both noradrenaline and 5-hydroxytryptamine. Responses to high K+ were also potentiated by neostigmine. However, high K+ elicited only small and irregular overflows of tritium from [3H]noradrenaline pre-incubated tissues, in contrast to the large overflow elicited by field stimulation. In addition guanethidine blocked responses to field stimulation but not those to high K+. This is consistent with the dose-related responses to high K+ being elicited postsynaptically. These results indicate that postsynaptic muscarinic receptors are involved in the potentiation by neostigmine of rat anococcygeus muscle responses to field stimulation or exogenous agonists, possibly by an action on receptor operated ion channels. Additional support for a postsynaptic site of action comes from the failure of neostigmine to potentiate tension responses to nerve or field stimulation in the chick expansor secundariorum, a muscle which is devoid of postsynaptic muscarinic receptors.

Characterization of the prejunctional adenosine receptors in the rat anococcygeus muscle.

Adenosine receptor agonists inhibited electrically-evoked contractions of the rat isolated anococcygeus muscle. The compounds tested were: N6-cyclopentyladenosine (CPA), N((S, trans)-2-hydroxycyclopentyl)adenosine (GR79236), the R- and S-isomers of phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamidoadenosine (NECA), ((2-(4-(2-carboxyethyl)phenyl)ethyl)amino)-N-ethylcarbox-amidoa denosine (CGS 21680) and N-((2-methylphenyl)methyl)adenosine (metrifudil). The rank order of agonist potency was: CPA = R-PIA = GR79236 = NECA >> S-PIA > metrifudil > CGS 21680, which is consistent with an effect mediated by adenosine A1 receptors. A similar rank order of potency was obtained for inhibition of electrically-evoked contractions of the guinea-pig ileum. However, there may be a lower receptor reserve in rat anococcygeus compared with the guinea-pig ileum, since higher concentrations of agonists were necessary to produce effects in the anococcygeus than in the guinea-pig ileum and S-PIA behaved as a partial agonist. The effect of NECA was antagonized in rat anococcygeus and guinea-pig ileum by the mixed A1/A2 receptor antagonist, 8-phenyltheophylline (pA2 values of 6.8 and 6.9, respectively). The selective A1-receptor antagonist, 8-cyclopentyl-1,3- dipropylxanthine (DPCPX), also blocked the inhibitory response to NECA in both tissues. Here, however, the pA2 values (9.6 and 8.6, respectively) were slightly but significantly different. These values confirm that the prejunctional adenosine receptors of the rat anococcygeus are of the A1 type, and suggest that they are similar but not necessarily identical to those of the guinea-pig ileum. The differing potencies of DPCPX as an antagonist of NECA between the preparations may reflect a tissue-dependent variation in sensitivity to this antagonist.

Does cocaine have a post-synaptic action on rat anococcygeus muscle?

Does cocaine have a post-synaptic action on rat anococcygeus muscle?

The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle.

The effects of antidepressants of tricyclic (amitriptyline, nortriptyline, protriptyline, doxepin, imipramine, and desipramine) and atypical (maprotiline, nomifensine, tandamine, viloxazine, CGP 6085A, and YM-08054-1) structures on contractile responses to exogenously applied acetylcholine and (-) noradrenaline were studied in rat isolated anococcygeus muscle previously incubated with 6-hydroxydopamine. Atropine, amitriptyline, protriptyline, doxepin, imipramine, maprotiline and nortriptyline inhibited contractile responses to acetylcholine whereas desipramine, nomifensine, tandamine, viloxazine, CGP 6085A and YM 08054-1 did not. The contractile responses to (-)-noradrenaline were inhibited by low concentrations of tricyclic antidepressants and by higher concentrations of the atypical agents. These results illustrate that, in the preparation, the order of potency of antidepressants as muscarinic and as postsynaptic alpha-adrenoceptor antagonists is similar. The ability of tricyclic, but not atypical agents, to increase the concentration of noradrenaline bound to postsynaptic alpha-adrenoceptors may be severely limited by the antagonistic effect these agents have at this receptor.

Evidence for alpha 2-adrenoceptor agonist activity of minoxidil.

The present investigation was undertaken to study the mechanism of action of minoxidil using various smooth muscle preparations. Minoxidil (4.7 x 10(-6) M to 4.7 x 10(-4) M) produced a concentration-dependent inhibition of field stimulation-evoked responses in rat anococcygeus muscle and vas deferens. The inhibition produced by minoxidil was antagonized by yohimbine (2.5 x 10(-7) M). Minoxidil (1.4 x 10(-5) M to 4.7 x 10(-4) M) also produced a concentration-dependent relaxation in oestrogen-primed potassium chloride-depolarized rat uterus. These responses were blocked not only by yohimbine but also by glibenclamide (2.02 x 10(-8) M). Our results suggest that minoxidil possesses alpha 2-adrenoceptor agonist activity in addition to potassium-channel-opening activity.

Iprindole potentiates responses to acetylcholine in the rat anococcygeus muscle.

Iprindole potentiates responses to acetylcholine in the rat anococcygeus muscle.

Effects of nomifensine on noradrenaline accumulation and contractile responses in the rat anococcygeus muscle.

Effects of nomifensine on noradrenaline accumulation and contractile responses in the rat anococcygeus muscle.

Low concentrations of cocaine and iprindole increase the neuronal accumulation of noradrenaline in the rat anococcygeus muscle

Low concentrations of cocaine and iprindole increase the neuronal accumulation of noradrenaline in the rat anococcygeus muscle

An inhibitory effect of histamine on the rat anococcygeus muscle.

An inhibitory effect of histamine on the rat anococcygeus muscle.

Effect of cocaine on tone and contractile responses to acetylcholine in the rat anococcygeus muscle.

Effect of cocaine on tone and contractile responses to acetylcholine in the rat anococcygeus muscle.