The effect of evocalcet on vagus nerve activity of the gastrointestinal tract in miniature pigs

Evocalcet is a novel calcimimetic agent with fewer gastrointestinal (GI) adverse effects compared to cinacalcet. Although it is thought that cinacalcet induces GI side effects through the direct stimulation of the calcium receptor (CaR) expressed in the GI tract, the differences in the direct stimulatory effects of these two drugs on the GI tract have not been reported. In this study, we analyzed the difference in the GI effects of these two calcimimetic agents using miniature pigs by detecting vagus nerve stimulation after oral administration of the agents. Although cinacalcet induced vomiting in miniature pigs, evocalcet never induced emetic symptoms. A significant increase in the vagus nerve action potentials was observed after the administration of cinacalcet. Although the increase of that after the administration of evocalcet was mild and not significant in comparison to that in the vehicle group, it was not significantly different from the vagus nerve action potentials after cinacalcet treatment.

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Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

Scientific Reports ◽

10.1038/s41598-021-91900-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jonathan A. Shulgach ◽

Dylan W. Beam ◽

Ameya C. Nanivadekar ◽

Derek M. Miller ◽

Stephanie Fulton ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Fibers ◽

The Body ◽

Evoked Responses ◽

Gi Tract ◽

Selective Stimulation ◽

Nerve Cuff ◽

Cuff Electrodes ◽

Nerve Cuff Electrodes ◽

Stimulation Of

AbstractDysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

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Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.259.6.l403 ◽

1990 ◽

Vol 259 (6) ◽

pp. L403-L409 ◽

Cited By ~ 18

Author(s):

A. C. Myers ◽

B. J. Undem ◽

D. Weinreich

Keyword(s):

Guinea Pig ◽

Vagus Nerve ◽

Action Potentials ◽

Receptor Activation ◽

Membrane Properties ◽

Constant Current ◽

Parasympathetic Ganglia ◽

Stimulation Of ◽

Passive Membrane

Active and passive membrane membrane properties of parasympathetic neurons were examined in vitro in a newly localized ganglion on the right bronchus of the guinea pig. Neurons could be classified as “tonic” or “phasic” based on their action potential discharge response to suprathreshold depolarizing constant current steps. Tonic neurons (39%) responded with repetitive action potentials sustained throughout the current step, whereas phasic neurons (61%) responded with an initial burst of action potentials at the onset of the step but then accommodated. Tonic and phasic neurons could not be differentiated by other active or passive membrane properties. Electrical stimulation of the vagus nerve elicited one to three temporally distinct fast nicotinic excitatory potentials, and tetanic stimulation of the vagus nerve evoked slow depolarizing (10% of neurons) and hyperpolarizing (25% of neurons) potentials; the latter was mimicked by muscarinic receptor activation. Similar slow and fast postsynaptic potentials were observed in both tonic and phasic neurons. We suggest neurons within the bronchial ganglion possess membrane and synaptic properties capable of integrating presynaptic stimuli.

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Development of neurotransmitter enzyme activity in the rat gastrointestinal tract

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1983.244.1.g58 ◽

1983 ◽

Vol 244 (1) ◽

pp. G58-G64

Author(s):

M. M. Heitkemper ◽

S. F. Marotta

Keyword(s):

Enzyme Activities ◽

Postnatal Period ◽

Male Rats ◽

Peak Activity ◽

Gi Tract ◽

Direct Stimulation ◽

Developmental Patterns ◽

Solid Diet ◽

Neurotransmitter Enzymes ◽

Stimulation Of

Acetylcholine and norepinephrine play important roles in determining gastrointestinal (GI) tract motility and secretion. At this time, however, little is known concerning the postnatal developmental patterns of the enzymes that synthesize and degrade these two neurotransmitters within the GI tract. The present study examined the developmental activities, expressed per gram protein per minute, of the cholinergic enzymes choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) and the adrenergic enzymes tyrosine hydroxylase (TH) and monoamine oxidase (MAO) in male rats between days 1 and 50. Seven anatomic segments of the GI tract were assayed for enzyme activities. In general, all four neurotransmitter enzymes were present throughout the length of the GI tract and increased during the early postnatal period. The synthesizing enzymes ChAT and TH displayed peak activity prior to day 21, while the degrading enzymes AChE and MAO continued to increase past day 21. Each enzyme exhibited segmental differences and unique postnatal developmental patterns. Such differences in enzyme activities may be related to developmental increases in neuronal density, hormonal factors, or direct stimulation of the GI tract by liquid and/or solid diet.

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Central Vasomotor Stimulation by Angiotensin

Clinical Science ◽

10.1042/cs0390239 ◽

1970 ◽

Vol 39 (2) ◽

pp. 239-245 ◽

Cited By ~ 105

Author(s):

C. M. Ferrario ◽

C. J. Dickinson ◽

J. W. McCubbin

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Internal Carotid ◽

Peripheral Resistance ◽

Systemic Arterial Pressure ◽

Direct Stimulation ◽

Vertebral Arteries ◽

Reflex Bradycardia ◽

The Difference ◽

Stimulation Of

1. When angiotensin was infused at low rates into the vertebral arteries of anaesthetized dogs, it raised the blood pressure. When infused at similar rates intravenously or into the internal carotid artery it either did not change blood pressure, or raised it only very slightly. The difference in response was highly significant over the range of 1–50 ng kg−1 min−1. 2. During intravenous infusion at higher rates, angiotensin usually produced the well-known reflex bradycardia and fall of cardiac output, but on infusion into the vertebral arteries it rapidly raised systemic arterial pressure, often increased heart rate, and usually produced a transient increase of cardiac output. 3. Angiotensin by both routes raised peripheral resistance, but noradrenaline, by contrast, produced the same response whether it was given into the vertebral arteries or into a vein. 4. These observations suggest that part of the pressor effect of intravenous angiotensin may be mediated by a direct stimulation of some part of the hind brain.

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Action potentials of isolated single muscle fibers recorded by potential-sensitive dyes.

The Journal of General Physiology ◽

10.1085/jgp.76.6.729 ◽

1980 ◽

Vol 76 (6) ◽

pp. 729-750 ◽

Cited By ~ 16

Author(s):

S Nakajima ◽

A Gilai

Keyword(s):

Action Potentials ◽

Light Transmission ◽

Surface Membrane ◽

Muscle Fibers ◽

Single Muscle ◽

Squid Axon ◽

Vertebrate Muscle ◽

Tubular System ◽

The Difference ◽

Stimulation Of

Light transmission changes upon massive stimulation of single muscle fibers of Xenopus were studied with the potential-sensitive nonpermeant dyes, merocyanine rhodanine (WW375) and merocyanine oxazolone (NK2367). Upon stimulation an absorption change (wave a) occurred, which probably represents the sum of action potentials in the transverse tubules and surface membrane. In WW375-stained fibers wave a is a decrease in transmission over the range of 630 to 730 nm (with NK2367, over the range of 590 to 700 nm) but becomes an increase outside this range, thus showing a triphasic spectral pattern. This spectrum differs from that of the squid axon, in which depolarization produces only an increase in transmission over the whole range of wavelengths (Ross et al. 1977. J. Membr. Biol. 33:141-183). When wave a was measured at the edge of the fiber to obtain more signal from the surface membrane, the spectrum did not seem to differ markedly from that obtained from the entire width of the fiber. Thus, the difference in the spectrum between the squid axon and the vertebrate muscle cannot be attributed to the presence of the tubular system.

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Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

10.1101/2021.02.19.431879 ◽

2021 ◽

Author(s):

Jonathan A. Shulgach ◽

Dylan W. Beam ◽

Ameya C. Nanivadekar ◽

Derek M. Miller ◽

Stephanie Fulton ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Fibers ◽

Vagal Afferents ◽

Evoked Responses ◽

Gi Tract ◽

Selective Stimulation ◽

Nerve Cuff ◽

Cuff Electrodes ◽

Nerve Cuff Electrodes ◽

Stimulation Of

AbstractDysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N=3) or ventral (N=3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that is was possible to selectively activate subpopulations of vagal afferents using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e. Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

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Electrophysiological study on nervous pathway from splanchnic nerve to vagus nerve in rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.244.6.r888 ◽

1983 ◽

Vol 244 (6) ◽

pp. R888-R890 ◽

Cited By ~ 2

Author(s):

A. Niijima

Keyword(s):

Vagus Nerve ◽

Action Potentials ◽

Electrophysiological Study ◽

Splanchnic Nerve ◽

Hepatic Branch ◽

Stimulation Of

Action potentials evoked by the stimulation of the hepatic branch of the splanchnic nerve were recorded from the peripheral cut end of the dorsal celiac branch of the vagus nerve in the rat. Action potentials were clearly demonstrated after averaging over 100 times by a computer. The observations indicate the existence of a nervous pathway from the hepatic branch of the splanchnic nerve to the dorsal celiac branch of the vagus nerve in the rat.

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Dependence of Intracellular End-Plate Action Potential on Adjacent Fiber Activity

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1956.187.1.199 ◽

1956 ◽

Vol 187 (1) ◽

pp. 199-202 ◽

Cited By ~ 1

Author(s):

Dexter M. Easton

Keyword(s):

Action Potential ◽

Action Potentials ◽

Rana Pipiens ◽

End Plate ◽

Lower Maximum ◽

The Difference ◽

Adductor Longus ◽

Intracellular Action ◽

Stimulation Of

Intracellular action potentials were recorded at the end plate and 1 mm away from it in small bundles of m. adductor longus of Rana pipiens during stimulation of the nerve. The end-plate spike reached a lower maximum and the repolarization was slower when compared with the spikes recorded 1 mm away. The difference was of the form expected from externally recorded impulses, and was much diminished when the number of fibers was reduced to two to three. It is suggested that asynchrony of the activity in adjacent fibers explains the lesser distortion of action potentials distant from the end plate.

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