Pharmacological modulation of cholinergic neurotransmission in guinea pig trachea in vitro

1980 ◽  
Vol 58 (7) ◽  
pp. 810-822 ◽  
Author(s):  
Thomas R. Jones ◽  
John T. Hamilton ◽  
Neville M. Lefcoe
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Low Frequency ◽  
Electrical Field Stimulation ◽  
Prostaglandin E ◽  
Cholinergic Nerves ◽  
Experimental Conditions ◽  
Cholinergic Neurotransmission ◽  
Stimulation Of

Electrical (field) stimulation of the isolated guinea pig trachea with normal intrinsic tone produced a biphasic response which consisted of an initial (cholinergic) contraction followed by (adrenergic and nonadrenergic) relaxation. Treatment of the tissue with the prostaglandin synthetase inhibitor indomethacin (2.8–5.6 μM) removed intrinsic tone and increased the responsiveness of the tissue to stimulation of cholinergic nerves and to exogenous acetylcholine. Indomethacin-relaxed tracheae were subsequently used to study cholinergic neurotransmission because under these experimental conditions only the contractile component of the response to electrical stimulation was observed. The β adrenoceptor blocking agents dl-propranolol and sotalol and the adrenergic neuron blocking agent guanethidine produced further enhancement of the contraction to electrical stimulation at low frequency (1–10 Hz). Prostaglandin E1, l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine selectively attenuated the contractions to electrical stimulation in concentrations which did not significantly alter the matched responses to exogenous acetylcholine. The selective depressant effect of l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine but not prostaglandin E1 were blocked by dl-propranolol or sotalol. The present results demonstrate that responses to stimulation of cholinergic nerves were altered by (1) prostaglandins and inhibitors of their synthesis, (2) neurally released adrenergic transmitter, and (3) exogenously added β adrenoceptor agonists. The possibility that prostaglandins and adrenergic neurotransmitter may modulate cholinergic neurotransmission at both pre- and post-junctional sites is hypothesized. It is proposed that more attention should be paid to the role of cholinergic transmission and its modulation in the studies of airway smooth muscle.

Nuclear Fos immunoreactivity in guinea pig myenteric neurons following activation of motor activity

1997 ◽  
Vol 273 (2) ◽  
pp. G498-G507 ◽  
Author(s):  
R. C. Ritter ◽  
M. Costa ◽  
S. H. Brookes
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Motor Activity ◽  
Muscle Tone ◽  
Smooth Muscle Contraction ◽  
Early Gene ◽  
Enteric Neurons ◽  
Experimental Conditions ◽  
Fos Expression

To identify enteric neurons activated during intestinal motor activity, we examined myenteric plexus of guinea pig small intestinal segments for expression of the immediate early gene product, Fos. Fos immunoreactivity was detected immunohistochemically following in vitro manipulations, which included distension, electrical stimulation, exposure to forskolin, and peristalsis. All of these manipulations induced neuronal Fos expression, which was prevented by tetrodotoxin, indicating that expression depended on nerve activity. Distension-induced Fos expression was blocked by omega-conotoxin and significantly reduced by hexamethonium, indicating that neurons expressing Fos immunoreactivity were activated synaptically. Blocking smooth muscle contraction with nicardipine reduced expression of neuronal Fos, suggesting that muscle tone influences neuronal activity. Calbindin-immunoreactive putative sensory neurons did not express Fos during distension, peristalsis, or exposure to forskolin and expressed Fos only weakly after strong electrical stimulation. Conversely, calretinin-immunoreactive ascending excitatory interneurons and longitudinal muscle motoneurons exhibited Fos immunoreactivity after all experimental manipulations. These results indicate that Fos expression can, with some caution, be used to identify classes of enteric neurons activated by different stimuli under various experimental conditions.

Lack of effect of botulinum toxin on nonadrenergic, noncholinergic inhibitory responses of the guinea pig fundus in vitro

1980 ◽  
Vol 58 (1) ◽  
pp. 88-92 ◽  
Author(s):  
M. L. Paul ◽  
M. A. Cook
Keyword(s):  
Botulinum Toxin ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Cholinergic Nerves ◽  
Electrical Field

The nonadrenergic, noncholinergic inhibitory (NAI) response of guinea pig fundic strip to electrical field stimulation was examined in the presence of botulinum toxin and tetrodotoxin. Tetrodotoxin completely abolished the NAI response while botulinum toxin did not alter it. It is concluded that the mediator of NAI responses is unlikely to be released with acetylcholine from cholinergic nerves or that such release would have to occur by a mechanism resistant to botulinum toxin.

Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue

1988 ◽  
Vol 254 (3) ◽  
pp. H459-H467 ◽  
Author(s):  
I. Saenz de Tejada ◽  
R. Blanco ◽  
I. Goldstein ◽  
K. Azadzoi ◽  
A. de las Morenas ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Electrical Stimulation ◽  
Muscle Tone ◽  
Corpus Cavernosum ◽  
Cholinergic Nerves ◽  
Smooth Muscle Tone ◽  
Cholinergic Neurotransmission ◽  
Stimulation Of

To investigate the role of cholinergic neurotransmission in erection, human penile corpus cavernosum tissue was studied. Electrical stimulation of strips of corpus cavernosum suspended in an organ chamber induced contractions and relaxations that were blocked by tetrodotoxin. The contractions also were blocked by bretylium and prazosin. Norepinephrine and phenylephrine contracted the isolated strips and this response was prevented by prazosin. Electrical stimulation-induced relaxations were enhanced by bretylium and physostigmine and partially blocked by atropine. The effect of atropine, but not that of physostigmine, was prevented by bretylium. Corporal strips contracted with norepinephrine relaxed to acetylcholine; this effect was blocked by atropine and enhanced by physostigmine. Strips lacking endothelium contracted normally with norepinephrine, but the relaxation caused by acetylcholine was virtually abolished. Thus endothelium lining the lacunar spaces within human corpus cavernosum is required for the relaxation caused by exogenous acetylcholine. There may be three neurotransmitter effector systems that control corpus cavernosum smooth muscle tone: adrenergic (excitatory), cholinergic (inhibitory), and nonadrenergic noncholinergic (inhibitory). Cholinergic nerves do not dilate or constrict directly the smooth muscle but may modulate other neuroeffector systems and/or the endothelium.

Neural regulation of 35SO4-macromolecule secretion from tracheal glands of ferrets

1984 ◽  
Vol 57 (2) ◽  
pp. 457-466 ◽  
Author(s):  
D. B. Borson ◽  
M. Charlin ◽  
B. D. Gold ◽  
J. A. Nadel
Keyword(s):  
Electrical Stimulation ◽  
Electrical Field Stimulation ◽  
Base Line ◽  
Field Stimulation ◽  
Cholinergic Nerves ◽  
Electrical Field ◽  
Molecular Weights ◽  
Submucosal Glands ◽  
Pharmacological Stimulation

Our goal was to determine what nervous mechanisms mediate the secretion of macromolecules from tracheal submucosal glands of ferrets. To do this, we studied the secretion of 35SO4-labeled macromolecules in vitro in response to electrical or pharmacological stimulation in the absence and presence of a specific nerve blocker and autonomic antagonists. We found that electrical field stimulation and the agonists acetylcholine, phenylephrine, terbutaline, and norepinephrine each cause secretion of radiolabeled materials. The molecular weights of the labeled materials released during base line and after electrical stimulation were greater than 1,000,000. The antagonists atropine, phentolamine, and propranolol alone prevented the responses to acetylcholine, phenylephrine, and terbutaline, respectively, without preventing responses to any other of these agonists or changing baseline secretion. Only phentolamine and propranolol together prevented the response to norepinephrine. Tetrodotoxin prevented the response to electrical stimulation but not the responses to the agonists. Each of the antagonists inhibited a significant portion of the response to electrical stimulation, but the combination of all three did not completely prevent secretion. We conclude that cholinergic nerves mediate secretion via muscarinic mechanisms, that adrenergic nerves mediate secretion via both alpha- and beta-adrenergic mechanisms, and that nonadrenergic-noncholinergic nerves mediate secretion via unidentified mechanisms.

Prejunctional inhibitory muscarinic receptors on cholinergic nerves in human and guinea pig airways

1988 ◽  
Vol 64 (6) ◽  
pp. 2532-2537 ◽  
Author(s):  
P. A. Minette ◽  
P. J. Barnes
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Pharmacological Characterization ◽  
Human Airways

We have investigated whether prejunctional inhibitory muscarinic receptors ("autoreceptors") exist on cholinergic nerves in human airways in vitro and whether guinea pig trachea provides a good model for further pharmacological characterization of these receptors. Pilocarpine was used as a selective agonist and gallamine as a selective antagonist of these autoreceptors. Acetylcholine (ACh) release from postganglionic cholinergic nerves was elicited by electrical field stimulation (EFS) (40 V, 0.5 ms, 32 Hz). In human bronchi, pilocarpine inhibited the contractile response to EFS in a dose-related fashion; the dose inhibiting 50% of the control contraction was 2.2 +/- 0.4 x 10(-7) (SE) M (n = 22), and the inhibition was 96% at 3 x 10(-5) M. The inhibitory effects of pilocarpine were antagonized by gallamine in a dose-related fashion. The results were qualitatively the same in the guinea pig. Gallamine significantly enhanced the contractile response to EFS in the guinea pig, whereas pirenzepine failed to do so, which suggests that M2-receptors are involved. We conclude that prejunctional muscarinic receptors that inhibit ACh release are present on cholinergic nerves in human airways and that guinea pig trachea is a good model for further pharmacological characterization of these receptors, which appear to belong to the M2-subtype.

scholarly journals Neural pathways regulating Brunner's gland secretion in guinea pig duodenum in vitro

2000 ◽  
Vol 279 (5) ◽  
pp. G910-G917 ◽  
Author(s):  
Beverley A. Moore ◽  
David Kim ◽  
Stephen Vanner
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Nerve Fibers ◽  
Neural Pathways ◽  
Brunner's Glands ◽  
Brunner’S Glands ◽  
Perivascular Nerves ◽  
Acinar Lumen ◽  
Stimulation Of

This study examined the neural pathways innervating Brunner's glands using a novel in vitro model of acinar secretion from Brunner's glands in submucosal preparations from the guinea pig duodenum. Neural pathways were activated by focal electrical stimulation and excitatory agonists, and videomicroscopy was used to monitor dilation of acinar lumen. Electrical stimulation of perivascular nerves evoked large dilations that were blocked by TTX (1 μM) or the muscarinic receptor antagonist 4-diphenylacetoxy- N-(2-chloroethyl)-piperidine hydrochloride (1 μM). The nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (100 μM) had no effect, and the nerve-evoked responses were not inhibited by hexamethonium (200 μM). Dilations were abolished in preparations from chronically vagotomized animals. Activation of submucosal ganglia significantly dilated submucosal arterioles but not Brunner's glands. Effects of electrical stimulation of perivascular and submucosal nerves were not altered by guanethidine. Capsaicin and substance P also dilated arterioles but had no effect on Brunner's glands. Cholinergic (choline acetyltransferase-immunoreactive) nerve fibers were found in Brunner's glands. These findings demonstrate that Brunner's glands are innervated by cholinergic vagal fibers but not by capsaicin-sensitive or intrinsic enteric nerves.

Prejunctional alpha 2-adrenoceptors inhibit acetylcholine release from cholinergic nerves in equine airways

1993 ◽  
Vol 265 (6) ◽  
pp. L565-L570 ◽  
Author(s):  
M. Yu ◽  
Z. Wang ◽  
N. E. Robinson
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Experimental Conditions ◽  
Adrenoceptor Antagonist ◽  
Cholinergic Neurotransmission ◽  
And Function

To determine the presence and function of alpha 2-adrenoceptors on cholinergic nerves innervating horse airway smooth muscle, the effects of some alpha 2-adrenoceptor agents on contractions of and acetylcholine (ACh) release from equine airway smooth muscle preparations were studied. Muscle contractions were elicited by either electrical field stimulation (EFS) or exogenous ACh. ACh release was induced by EFS and measured by high-pressure liquid chromatography and electrochemical detection. The alpha 2-adrenoceptor agonists clonidine (10(-7) to 10(-5) M) and UK-14,304 (10(-8) to 10(-6) M) concentration dependently inhibited ACh release and the contractile response to EFS but not the response to exogenous ACh. This inhibition was attenuated by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan but not by the alpha 1-adrenoceptor antagonist prazosin. These results indicate that alpha 2-adrenoceptors exist on cholinergic nerves innervating equine airway smooth muscle, and activation of these receptors inhibits cholinergic neurotransmission. The observation that yohimbine alone had little effect on the contractile response to EFS suggests that, under these experimental conditions, endogenous norepinephrine had no influence on tracheal cholinergic neurotransmission via prejunctional alpha 2-adrenoceptors.

scholarly journals Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework

2021 ◽  
Vol 11 (5) ◽  
pp. 639
Author(s):  
David Bergeron ◽  
Sami Obaid ◽  
Marie-Pierre Fournier-Gosselin ◽  
Alain Bouthillier ◽  
Dang Khoa Nguyen
Keyword(s):  
Chronic Pain ◽  
Electrical Stimulation ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Brain Lesion ◽  
Low Frequency ◽  
Posterior Insula ◽  
Deep Brain ◽  
Stimulation Of

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

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