Methods for the Examination of Ganglion-Blocking Activity

Gyermek, László

doi:10.1007/978-3-642-67397-9_4

Cited by 15 publications

(7 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition was absent or only very weak. In contrast, application of the nicotinic agonist DMPP (Chen et al, 1951;see Table 2 in Gyermek, 1980) (1 mM; n = 7) caused excitation followed by prolonged inhibition (Fig. 2B).…”

Section: Applicationmentioning

confidence: 87%

Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro

McCormick¹,

Prince²

1987

J. Neurosci.

View full text Add to dashboard Cite

The actions of ACh in the medial habenular nucleus (MHb) were investigated using extra- and intracellular recording techniques in guinea pig thalamic slice maintained in vitro. Applications of ACh to MHb neurons resulted in rapid excitation followed by inhibition. Neither of these responses was abolished by blockade of synaptic transmission, indicating that they are consequences of ACh action directly on MHb cells. Local applications of the nicotinic agonists nicotine and cytisine caused long-lasting excitation, while applications of another nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium caused both the excitatory and inhibitory responses. Applications of the muscarinic agonists DL-muscarine and acetyl-beta-methylcholine did not consistently cause either the excitatory or inhibitory response. Adding the nicotinic antagonist hexamethonium to the bathing medium blocked both the excitatory and inhibitory ACh responses, while addition of the muscarinic antagonists atropine or scopolamine had no effect. These results indicate that the effects of ACh on MHb neurons are mediated by nicotinic receptors. Intracellular recordings revealed that ACh or nicotine cause an increase in membrane conductance associated with depolarizations that had an average reversal potential of -16 to -11 mV. These results indicate that the ACh-induced excitation is due to an increase in membrane cation conductance. The inhibitory response that follows ACh-induced depolarization and repetitive firing was associated with a hyperpolarization and an increase in membrane conductance. Similar postexcitatory inhibition could also be elicited by direct depolarization or by applications of glutamate, indicating that the hyperpolarizing response to ACh may be an endogenous postexcitatory potential that is not directly coupled to activation of nicotinic receptors. These results suggest that cholinergic transmission in the MHb may be largely of the nicotinic type. This nucleus may be of one of the major regions of the nervous system through which nicotine mediates its central effects.

show abstract

Section: Applicationmentioning

confidence: 87%

Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro

McCormick¹,

Prince²

1987

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The blocking action of mecamylamine is exerted on all native subtypes of nAChRs despite their different subunit composition (Connolly et al, 1992). In vivo mecamylamine lowers blood pressure and can prevent seizures induced experimentally with the use of nicotine (Gyermek, 1980). In view of this widespread action, which remains, however, highly selective against nAChRs, mecamylamine is commonly used to probe the role of such receptors in central and peripheral synaptic transmission processes.…”

mentioning

confidence: 99%

Rapid Relief of Block by Mecamylamine of Neuronal Nicotinic Acetylcholine Receptors of Rat Chromaffin Cells In Vitro: An Electrophysiological and Modeling Study

et al. 2000

View full text Add to dashboard Cite

The mechanism responsible for the blocking action of mecamylamine on neuronal nicotinic acetylcholine receptors (nAChRs) was studied on rat isolated chromaffin cells recorded under whole-cell patch clamp. Mecamylamine strongly depressed (IC(50) = 0.34 microM) inward currents elicited by short pulses of nicotine, an effect slowly reversible on wash. The mecamylamine block was voltage-dependent and promptly relieved by a protocol combining membrane depolarization with a nicotine pulse. Either depolarization or nicotine pulses were insufficient per se to elicit block relief. Block relief was transient; response depression returned in a use-dependent manner. Exposure to mecamylamine failed to block nAChRs if they were not activated by nicotine or if they were activated at positive membrane potentials. These data suggest that mecamylamine could not interact with receptors either at rest or at depolarized level. Other nicotinic antagonists like dihydro-beta-erythroidine or tubocurarine did not share this action of mecamylamine although proadifen partly mimicked it. Mecamylamine is suggested to penetrate and block open nAChRs that would subsequently close and trap this antagonist. Computer modeling indicated that the mechanism of mecamylamine blocking action could be described by assuming that 1) mecamylamine-blocked receptors possessed a much slower, voltage-dependent isomerization rate, 2) the rate constant for mecamylamine unbinding was large and poorly voltage dependent. Hence, channel reopening plus depolarization allowed mecamylamine escape and block relief. In the presence of mecamylamine, therefore, nAChRs acquire the new property of operating as coincidence detectors for concomitant changes in membrane potential and receptor occupancy.

show abstract

“… 5 Mecamylamine hydrochloride is a secondary amine and a well characterized post-ganglionic sympathetic system inhibitor that has been shown to block nicotine-induced stimulation of nAChRs and was extensively used as an antihypertensive. 16 – 19 Studies in mammalian brain and amphibian neuromuscular tissue demonstrated that mecamylamine is a noncompetitive inhibitor that binds to the nAChR ion channel region and decreases the longevity of channel opening rather than by blocking nicotine binding. 20 , 21 Mecamylamine is a highly lipophilic small molecule with an excellent biodistribution profile that makes it an excellent candidate for topical administration.…”

mentioning

confidence: 99%

The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity

Hackett

Seidel

Abraham

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeTo investigate the role of nicotinic acetylcholine receptors (nAChRs) in retinal vascular development and ischemia-induced retinal neovascularization (NV).MethodsThe expression of nAChR subtypes and VEGF signaling pathway components was assessed in mice with and without oxygen-induced ischemic retinopathy by comparing expression levels at postnatal day (P) 14 and P17 in mice exposed to 75% oxygen from P7 to P12 and returned to room air versus mice pups that were exposed to ambient oxygen levels during the same period. The effect of topical or intraocular injection of mecamylamine, a nonspecific nAChR antagonist, or targeted deletion of α7- or α9-nAChRs on ischemia-induced retinal NV was determined by comparing the amount of retinal NV at P17 in these mice versus appropriate controls.ResultsThe expression of nAChR subunits and components of the VEGF signaling pathways was increased in ischemic retina. Topical application or intraocular injection of mecamylamine decreased retinal NV in this model. Mecamylamine had no effect on normal retinal vascular development or on revascularization of the central retinal area of nonperfusion in mice with ischemic retinopathy. Targeted deletion of α9, but not α7, nAChR receptor subunits reduced retinal NV in mice with ischemic retinopathy.ConclusionThese data suggest that nAChR signaling, primarily through the α9 nAChR subunit, contributes to ischemia-induced retinal NV, but not retinal vascular development. Mecamylamine or a specific α9 nAChR antagonist could be considered for treatment of retinopathy of prematurity and other ischemic retinopathies.

show abstract

Methods for the Examination of Ganglion-Blocking Activity

Cited by 15 publications

References 115 publications

Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro

Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro

Rapid Relief of Block by Mecamylamine of Neuronal Nicotinic Acetylcholine Receptors of Rat Chromaffin Cells In Vitro: An Electrophysiological and Modeling Study

The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity

Contact Info

Product

Resources

About