Pharmacological differences between two muscarinic responses of the rat superior cervical ganglion <i>in vitro</i>

Newberry, Nigel R.; Priestley, Tony

doi:10.1111/j.1476-5381.1987.tb11386.x

Cited by 54 publications

(19 citation statements)

References 38 publications

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“…Adenosine or 3,B-MeATP but not ATP significantly increased the depolarization produced by application of 10 JAM GABA (Table 2). (Brown et al, 1980;Newberry & Priestley, 1987;Newberry & Connolly, 1989) and adenosine-induced hyperpolarization of the rat SCG (Connolly & Stone, 1993b). Hyperpolarizations of the rat SCG caused by adenosine were reported to be dependent upon [Ca2"], but are not due to an interaction with calcium channels as calcium channel antagonists were ineffective or enhanced the response to adenosine (Connolly & Stone, 1993b).…”

Section: Resultsmentioning

confidence: 99%

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Connolly

Harrison

Stone

1993

British J Pharmacology

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1 Using a grease-gap technique, we have investigated the effects of purine and pyrimidine nucleotides on the d.c. potential of the rat isolated superior cervical ganglion (SCG). 2 Of the purines tested, adenosine, adenosine 5'-triphosphate (ATP), P,y-methylene-adenosine 5'-triphosphate (P,y-MeATP) at up to 300 gM produced concentration-dependent hyperpolarizations, whereas 2-methyl-thio-ATP (2-Me.S.ATP) and a,p-methylene-ATP (a,,B-MeATP) depolarized ganglia. Of the pyrimidines tested, uridine 5'-triphosphate (UTP) produced concentration-dependent depolarizations and cytosine 5'-triphosphate (CTP) at 1000 tLM produced considerably smaller but significant depolarizations. In contrast uridine 5'-monophosphate (UMP) at 1000 AM hyperpolarized ganglia. The relative order of potency of purines and pyrimidines to depolarize ganglia was:-UTP> az,-MeATP>> CTP> 2-Me.S.ATP and to hyperpolarize ganglia was:-adenosine = P,By-MeATP> ATP> UMP.3 The ability of purines and pyrimidines to alter the depolarizing response caused by muscarine and of purines to alter depolarization induced by y-aminobutyric acid (GABA) was determined. The relative order of potency of nucleotides in depressing submaximal depolarization caused by muscarine (100 nM) was: adenosine = ATP>P,y-MeATP whereas 2-Me.S.ATP, a,4-MeATP and UTP did not significantly alter depolarization caused by muscarine. At 100ZM 3,Ty-MeATP and adenosine but not ATP potentiated GABA-induced depolarizations. 4 Hyperpolarizations caused by adenosine, ATP, P,y-MeATP and UMP and depolarizations caused by aj-MeATP were enhanced in medium containing reduced concentrations of calcium (0.1 mM) and potassium (2 mM). In this medium 8-phenyltheophylline abolished hyperpolarizations caused by adenosine and reversed hyperpolarizations caused by ATP into depolarizations. Suramin (300 tLM), a P2-purinoceptor antagonist, significantly reduced the depolarizing response caused by a,t-MeATP and significantly increased hyperpolarizations caused by ATP and ,B,-MeATP. Suramin (300 AM) did not significantly alter depolarizations caused by l,l-dimethyl-4-phenylpiperazinium (10 ILM), potassium (3 mM) or muscarine (100 nM) and significantly potentiated depolarizations caused by UTP (100IM).5 It is concluded that the rat SCG contains PI-purinoceptors that hyperpolarize the ganglion and diminish sensitivity to muscarine, and P2X-purinoceptors that depolarize the SCG. There is also some evidence to suggest the presence of receptors for UTP, i.e., pyrimidinoceptors, which depolarize SCG neurones.

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Section: Resultsmentioning

confidence: 99%

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Connolly

Harrison

Stone

1993

British J Pharmacology

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“…Each superior cervical ganglion (SCG, sometimes called the cranial cervical ganglion in the guinea-pig) was desheathed and submerged in a three compartment bath with the ganglion body in the central compartment and the pre-and postganglionic trunks (the cervical sympathetic trunk and the internal carotid nerve, respectively) protruding through greased gaps into the outer two compartments (Newberry & Priestley, 1987;Newberry, 1988). The central compartment (volume ca.…”

Section: Methodsmentioning

confidence: 99%

Evidence that the 5‐HT₃ receptors of the rat, mouse and guinea‐pig superior cervical ganglion may be different

Newberry

Cheshire

Gilbert

1991

British J Pharmacology

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1 Using grease-gap recordings from the isolated superior cervical ganglion of mouse, rat and guinea-pig, we have compared the depolarization evoked by 5-hydroxytryptamine (5-HT) with that evoked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-Me-5-HT). 2 The maximum depolarization induced by 2-Me-5-HT was smaller than that induced by 5-HT in all three species, and particularly in the guinea-pig. 3 The 5-HT2 receptor antagonist ketanserin (1 UM) caused a clear rightward shift of the dose-response curve to 5-HT on the guinea-pig ganglion, but not on the mouse or rat ganglion. Spiperone (0.03pM) had a quantitatively similar action to ketanserin (O.1pM) on the 5-HT dose-response curve of the guinea-pig ganglion. Ketanserin had no significant effect on the dose-response curve to 2-Me-5-HT on any of these ganglia. 4 Using 2-Me-5-HT as the agonist, we determined the pA2 values for two 5-HT3 receptor antagonists. The potency of ICS 205-930 varied by approximately 100 fold between the species and that of (+)-tubocurarine varied by over 1000 fold. The differences in the pA2 values of these compounds varied independently among the species. 5 We conclude that 5-HT3 receptors are present on the superior cervical ganglion from the rat, mouse and guinea-pig, but these receptors may be pharmacologically distinct from each other. In addition, the depolarization of the guinea-pig superior cervical ganglion by low concentrations of 5-HT is largely mediated by ketanserin-sensitive receptors.

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“…They are divided into five pharmacological subtypes, M 1 -M 5 . MFI produces depolarization in rat cervical ganglion cells (Newberry and Priestley, 1987;Roberts and Newberry, 1990) by stimulation of receptors that produce closure of an inwardly rectifying potassium channel current known as the M-current (Caulfield et al, 1994). We have shown here that MFI also produces depolarization and inhibition of voltageactivated potassium currents in A. suum.…”

Section: Discussionmentioning

confidence: 70%

“…We therefore selected 5-methylfurmethiodide (MFI, Fig. 1A) which is a potent mammalian muscarinic agonist (Newberry and Priestley, 1987) for further testing. In this paper we show that MFI in A. suum has four effects: i) it is a weak nicotinic agonist; ii) it opens mecamylamineresistant non-selective cation channels; iii) it inhibits opening of voltage-activated potassium channels; and iv) it increases the threshold for activation of calcium channels.…”

Section: Introductionmentioning

confidence: 99%

Effects of the muscarinic agonist, 5-methylfurmethiodide, on contraction and electrophysiology of Ascaris suum muscle

Trailovic

Verma

Clark

et al. 2008

International Journal for Parasitology

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Contraction and electrophysiological effects of 5-methylfurmethiodide (MFI), a selective muscarinic agonist in mammals, were tested on Ascaris suum muscle strips. In a contraction assay, MFI produced weak contraction and was less potent than levamisole and acetylcholine. Atropine (3 µM) a nonselective muscarinic antagonist in mammalian preparations, did not affect contractions produced by MFI. Mecamylamine (3 µM) a nicotinic antagonist in A. suum preparations, blocked the MFI contractions indicating that MFI had weak nicotinic agonist actions. In two-micropipette currentclamp experiments MFI, at concentrations greater than 10 µM, produced concentration-dependent depolarizations and small increases in membrane conductance. The depolarizing effects were not abolished by perfusing the preparation in a calcium-free Ascaris Ringer solution to block synaptic transmission, suggesting that MFI effects were mediated by receptors on the muscle and were calcium-independent. A high concentration of mecamylamine, 30 µM, only reduced the depolarizing responses by 42%, indicating that MFI also had effects on non-nicotinic receptors. Three nonnicotinic effects in the presence of 30 µM mecamylamine were identified using voltage-clamp techniques: i) MFI produced opening of mecamylamine-resistant non-selective-cation channel currents; ii) MFI inhibited opening of voltage-activated potassium currents; and iii) MFI increased the threshold of voltage-activated calcium currents. We suggest that a drug that is more selective for voltage-activated potassium currents, without effects on other channels like MIF, may be exploited pharmacologically as a novel anthelmintic or as an agent to potentiate the action of levamisole. In a larval migration assay we demonstrated that 4-aminopyridine (4-AP: a potassium channel blocker) potentiated the effects of levamisole but MFI did not.

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Pharmacological differences between two muscarinic responses of the rat superior cervical ganglion in vitro

Cited by 54 publications

References 38 publications

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Evidence that the 5‐HT₃ receptors of the rat, mouse and guinea‐pig superior cervical ganglion may be different

Effects of the muscarinic agonist, 5-methylfurmethiodide, on contraction and electrophysiology of Ascaris suum muscle

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Pharmacological differences between two muscarinic responses of the rat superior cervical ganglion in vitro

Cited by 54 publications

References 38 publications

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion

Evidence that the 5‐HT3 receptors of the rat, mouse and guinea‐pig superior cervical ganglion may be different

Effects of the muscarinic agonist, 5-methylfurmethiodide, on contraction and electrophysiology of Ascaris suum muscle

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Evidence that the 5‐HT₃ receptors of the rat, mouse and guinea‐pig superior cervical ganglion may be different