Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

Parkman, Henry P.; Pagano, Anthony P.; Ryan, James P.

doi:10.1016/s0016-5085(98)83341-6

Cited by 9 publications

(11 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predominance of muscarinic M 1 autofacilitation was observed when low stimulation frequencies (5 Hz) were used, a situation that coincided with the appearance of small amounts of extracellular adenosine activating inhibitory A 1 receptors (cf. Correia‐de‐Sá et al ., 1996). We have now demonstrated that, besides its physiologically relevant inhibitory role, tonic adenosine A 1 receptors function also prevents the muscarinic M 2 negative feedback mechanism becoming active.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the functional role of muscarinic modulation on smooth muscle preparations (e.g. urinary bladder, gallbladder) showed that both M 1 ‐facilitatory and M 2 ‐inhibitory receptors can be colocalized in cholinergic nerves (Somogyi et al ., 1994; Parkman et al ., 1999). Using muscarinic antagonists that discriminate between facilitatory M 1 and inhibitory M 2 receptors, respectively, MT‐7 (0.1–1 n m ) or pirenzepine (1–30 n m ) and AF‐DX 116 (0.01–10 µ m ), we could demonstrate that two different subtypes of muscarinic receptors mediate a dual neuromodulatory role at the rat neuromuscular junction.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals

Oliveira

Timóteo

Correia‐de‐Sá

2002

Eur J of Neuroscience

View full text Add to dashboard Cite

The crosstalk between adenosine and muscarinic autoreceptors regulating evoked [3H]-acetylcholine ([3H]-ACh) release was investigated on rat phrenic nerve-hemidiaphragm preparations. Motor nerve terminals possess facilitatory M1 and inhibitory M2 autoreceptors that can be activated by McN-A-343 (1-30 microm) and oxotremorine (0.3-100 microm), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm-10 microm), caused a biphasic (inhibitory/facilitatory) effect, indicating that M1-facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF-DX 116-sensitive M2 receptors was partially attenuated, as pretreatment with M1 antagonists, muscarinic toxin 7 (MT-7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A2A-adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN-A-343-induced facilitation into a small inhibitory effect. Conversely, the A1-receptor agonist, R-N6-phenylisopropyl adenosine (R-PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN-A-343. Synergism between A2A and M2 receptors is regulated by a reciprocal interaction with facilitatory M1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz-bursts, facilitation (M1) of [3H]-ACh release by McN-A-343 disappeared, while the inhibitory (M2) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A2A receptors, as it was precluded by the selective A2A receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A1 receptors. During high frequency bursts, tonic activation of A2A receptors promotes M2 autoinhibition by braking the M1 receptor operated counteraction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals

Oliveira

Timóteo

Correia‐de‐Sá

2002

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…In airway, the release of ACh from guinea‐pig mesenteric and submucous plexus neurons is inhibited by prejunctional M 1 receptor (Kawashima et al ., 1988; Kilbinger et al ., 1993; Dietrich & Kilbinger, 1995). It is also reported that prejunctional M1 receptors act as excitatory autoreceptors which facilitate the ACh release in rat urinary bladder (Somogyi & de Groat, 1999), guinea‐pig gallbladder (Parkman et al ., 1999) and guinea‐pig ileum (Izzo et al ., 1999). Therefore, muscarinic M1 receptors on different locations may serve distinct physiological functions.…”

Section: Discussionmentioning

confidence: 99%

An electrophysiological study of muscarinic and nicotinic receptors of rat paratracheal ganglion neurons and their inhibition by Z‐338

Kanemoto

Ishibashi

Doi

et al. 2002

British J Pharmacology

View full text Add to dashboard Cite

1 To study the mechanisms involved in the action of Z-338, a newly synthesized gastroprokinetic agent, experiments were performed with the paratracheal ganglion cells acutely dissociated from 2-week-old Wistar rats. The e ects of Z-338 on both nicotinic and muscarinic responses of the ganglion cells were studied by nystatin perforated patch recording con®guration under the currentand voltage-clamp conditions. 2 Acetylcholine (ACh) or nicotine, and muscarine or oxotremorine-M (OX-M) induced membrane depolarization with rapid and slow time courses respectively, followed by repetitive generation of action potentials in the ganglion cell. Corresponding to the membrane depolarization induced by cholinergic agents, ACh induced biphasic inward currents with rapid and slow time courses under the voltage-clamp condition. Nicotine and muscarine or OX-M evoked inward currents with rapid and slow time courses, respectively. The rapid and slow inward currents were accompanied by increase and decrease in the membrane conductance, respectively. In addition, OX-M dosedependently suppressed the M-type K + current evoked in response to hyperpolarizing voltage-steps from V H of 725 mV to 750 mV, indicating that the activation of muscarinic acetylcholine receptors inhibits M-type K + current, thus inducing inward current in the ganglion cell. 3 Z-338 competitively suppressed the inward currents induced by OX-M through M 1 ACh receptor, and uncompetitively suppressed the currents induced by nicotine. 4 The inhibitory actions of Z-338 on the membrane depolarization and corresponding inward currents mediated by M 1 -muscarinic and neuronal nicotinic ACh receptors in the isolated ganglion cells were discussed in relation to the inhibitory actions on autoreceptors in the parasympathetic nerve terminals, which would explain the gastroprokinetic actions of Z-338.

show abstract

“…The reported M1 subtype receptor antagonist pirenzepine, the M2 antagonist methoctramine, or the M4 receptor antagonist tropicamide did not have appreciable effects (Table 1). This suggests the cholinergic contractile response of ACh and EFS are primarily mediated through the M3 muscarinic receptor subtype 9 .…”

Section: General Findingsmentioning

confidence: 99%

“…UK 14,304 and citalopram hydrobromide were obtained from Tocris Cookson Inc. (Ellesville, MO, USA). The following muscarinic receptor subtype antagonists were used 9 : pirenzepine dihydrochloride, a M1 receptor antagonist (Sigma Chemical Co.); methoctramine hydrochloride, a M2 receptor antagonist (Research Biochemicals International, Natick, MA, USA); 4‐diphenylacetoxy‐ N ‐methylpiperidine (4‐DAMP) methiodide, a M3 receptor antagonist (Research Biochemicals International); and tropicamide, a reported M4 receptor antagonist (Sigma Chemical Co.).…”

Section: Compoundsmentioning

confidence: 99%

Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility

James

Ryan

Parkman

2004

Neurogastroenterology Motil

View full text Add to dashboard Cite

To determine if and how clonidine and tricyclic antidepressants affect gastric contractility. Guinea pig fundic and antral circular muscle strips were studied in vitro. The effects of clonidine or amitriptyline added in graded concentrations on contractions to electric field stimulation (EFS), acetylcholine (ACh), and SP in the presence of N(epsilon)-nitro-l-arginine methyl ester (l-NAME) were studied. EFS produced frequency dependent contractions of fundic and antral muscle that were abolished by atropine or tetrodotoxin (TTX). ACh contractions were abolished by atropine but not TTX. Clonidine reduced contractile response to EFS but had no effect on ACh contractions. The threshold concentration of clonidine to inhibit EFS contractions was lower in the fundus than in the antrum. Amitriptyline reduced contractions to both EFS and ACh but not to SP. The threshold concentration of amitriptyline to inhibit EFS contractions was lower in the antrum than in the fundus. Both clonidine and amitriptyline affect gastric contractility. At threshold concentrations, clonidine affects fundic contractility whereas amitriptyline affects antral contractility. Clonidine affects gastric contractility in response to EFS but not to ACh, suggesting alpha-2 receptors on cholinergic nerves that reduce ACh release. Amitriptyline inhibits gastric contractility to EFS and ACh suggesting an inhibitory muscle effect.

show abstract

Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

Cited by 9 publications

References 17 publications

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals

An electrophysiological study of muscarinic and nicotinic receptors of rat paratracheal ganglion neurons and their inhibition by Z‐338

Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility

Contact Info

Product

Resources

About

Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

Cited by 9 publications

References 17 publications

Modulation by adenosine of both muscarinic M1‐facilitation and M2‐inhibition of [3H]‐acetylcholine release from the rat motor nerve terminals

Modulation by adenosine of both muscarinic M1‐facilitation and M2‐inhibition of [3H]‐acetylcholine release from the rat motor nerve terminals

An electrophysiological study of muscarinic and nicotinic receptors of rat paratracheal ganglion neurons and their inhibition by Z‐338

Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility

Contact Info

Product

Resources

About

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals

Modulation by adenosine of both muscarinic M₁‐facilitation and M₂‐inhibition of [³H]‐acetylcholine release from the rat motor nerve terminals