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American Journal of Physiology.... Apr 2013Regional variation in sweating over the human body is widely recognized yet variation in vasomotor responses and mechanisms causing this variation remain unclear. This...
Regional variation in sweating over the human body is widely recognized yet variation in vasomotor responses and mechanisms causing this variation remain unclear. This study aimed to explore the relation between regional sweating rates (RSR) and skin blood flow (SkBF) responses to thermal and pharmacological stimuli in young, healthy subjects. In nine subjects (23 ± 3 yr), intradermal microdialysis (MD) probes were inserted into the ventral forearm, abdomen, thigh, and lower back and perfused with lactated Ringer solution. RSR over each MD membrane were measured using ventilated capsules with a laser Doppler probe housed in each capsule for measurement of red cell flux (laser Doppler flux, LDF) as an index of SkBF. Subjects completed a whole body heating protocol to 1°C rise in oral temperature and an acetylcholine dose response (ACh 1 × 10(-7)-0.1 M; mean skin temperature 34°C). Maximal LDF were obtained at the end of both protocols (50 mM sodium nitroprusside).During heating RSR varied among sites (P < 0.0001) and was greater on the back versus other sites (P < 0.05), but LDF was similar between sites (P = 0.343). RSR and SkBF showed a strong relation during initial (arm: r = 0.77 ± 0.09, thigh: r = 0.81 ± 0.08, abdomen: r = 0.89 ± 0.04, back: r = 0.86 ± 0.04) but not latter stages of heating. No differences in RSR (P = 0.160) or SkBF (LDF, P = 0.841) were observed between sites during ACh perfusion. Taken together, these data suggest that increases in SkBF are necessary to initiate and increase sweating, but further rises in RSR are not fully dependent on SkBF in a dose-response manner. Furthermore, RSR cannot be explained by cholinergic sensitivity or variation in SkBF.
Topics: Acetylcholine; Adult; Dose-Response Relationship, Drug; Female; Hot Temperature; Humans; Male; Regional Blood Flow; Skin; Sweating; Vasodilator Agents; Young Adult
PubMed: 23389110
DOI: 10.1152/ajpregu.00514.2012 -
Proceedings of the National Academy of... Mar 2003Neurotransmitters are stored in synaptic vesicles, where they have been assumed to be in free solution. Here we report that in Torpedo synaptic vesicles, only 5% of the...
Neurotransmitters are stored in synaptic vesicles, where they have been assumed to be in free solution. Here we report that in Torpedo synaptic vesicles, only 5% of the total acetylcholine (ACh) or ATP content is free, and that the rest is adsorbed to an intravesicular proteoglycan matrix. This matrix, which controls ACh and ATP release by an ion-exchange mechanism, behaves like a smart gel. That is, it releases neurotransmitter and changes its volume when challenged with small ionic concentration change. Immunodetection analysis revealed that the synaptic vesicle proteoglycan SV2 is the core of the intravesicular matrix and is responsible for immobilization and release of ACh and ATP. We suggest that in the early steps of vesicle fusion, this internal matrix regulates the availability of free diffusible ACh and ATP, and thus serves to modulate the quantity of transmitter released.
Topics: Acetylcholine; Adenosine Triphosphate; Animals; Electric Organ; Gels; In Vitro Techniques; Microscopy, Atomic Force; Models, Molecular; Neurotransmitter Agents; Permeability; Synaptic Vesicles; Torpedo
PubMed: 12629223
DOI: 10.1073/pnas.0336914100 -
Acta Dermato-venereologica Nov 1995The mediators eliciting pruritus in atopic eczema are a matter of discussion, since several substances may be involved and histamine is unlikely to be the main agent....
The mediators eliciting pruritus in atopic eczema are a matter of discussion, since several substances may be involved and histamine is unlikely to be the main agent. Hence, in this study we examined the cutaneous sensations and vascular reactions in 15 patients with atopic eczema and in 15 non-atopic subjects after i.c. injection of acetylcholine (Ach, 0,5 M, 20 microliter) or buffered saline, respectively. The sensory perceptions were rated by a visual analogue scale (VAS) as to quality and intensity, and the vascular reactions were monitored by laser Doppler flowmetry and evaluated planimetrically as to flare and wheal extension. The flares and wheals in both groups were similar; yet the cutaneous sensations significantly differed, since all patients with atopic eczema complained of "pure" itching after Ach-injection, whereas the controls reported a burning pain. The patients with atopic eczema started their ratings significantly earlier and rated significantly longer than the controls. Our results provide evidence that Ach may play an important role in the etiology of pruritus in atopic eczema patients.
Topics: Acetylcholine; Adolescent; Adult; Dermatitis, Atopic; Female; Humans; Injections, Intradermal; Laser-Doppler Flowmetry; Male; Neurotransmitter Agents; Pruritus; Skin
PubMed: 8651018
DOI: 10.2340/0001555575434436 -
Biomedical Research (Tokyo, Japan) 2023To clarify the role of the aquaporin 5 (AQP5) in salivary secretion, we evaluated acetylcholine (ACh)-induced secretion in Sprague-Dawley (SD) rats, rats expressing a...
To clarify the role of the aquaporin 5 (AQP5) in salivary secretion, we evaluated acetylcholine (ACh)-induced secretion in Sprague-Dawley (SD) rats, rats expressing a low level of AQP5 protein (AQP5/low SD) which developed from SD rats, and Wistar/ST rats. The salivary secretion in AQP5/low SD rats in response to infusions of low-dose ACh (60-120 nmol/min) was 27-42% of that in SD rats. By contrast, Wistar/ST rats exhibited comparable secretion to that of SD rats in response to low-doses ACh, despite their low-level expression of AQP5. Experiments using spectrofluorometry and RT-PCR demonstrated no differences in the ACh-induced Ca responses or the mRNA expression of muscarinic receptor, Cl channel, or cotransporter between these strains. These findings imply that factors other than the function of salivary acinar cells regulates the secretion in response to weak stimuli. Monitoring of the hemodynamics in the submandibular gland revealed that low-doses ACh induced different patterns of the fluctuations in the blood flow in these strains. The blood flow decreased below the resting level in AQP5/low SD rats, but remained mostly above the resting level in Wistar/ST rats. The present study reveals that the contribution of AQP5-dependent transport of water is altered by stimulus intensity and blood flow.
Topics: Rats; Animals; Saliva; Aquaporin 5; Acetylcholine; Rats, Wistar; Rats, Sprague-Dawley; Hemodynamics
PubMed: 37005283
DOI: 10.2220/biomedres.44.51 -
The Journal of Physiology Jun 1958
Topics: Acetylcholine; Choline O-Acetyltransferase; Cytoplasm; Esterases; Hemorrhage; Synaptic Transmission
PubMed: 13564428
DOI: 10.1113/jphysiol.1958.sp006008 -
Advanced Science (Weinheim,... Jun 2021Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant...
Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion-conducting membrane out to the local implanted area. This solvent-flow-free "dry" delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co-ion is presented. By switching acetylcholine's associated co-ion from chloride to carboxylate co-ions as well as sulfopropyl acrylate-based polyanions, steady-state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices.
Topics: Acetylcholine; Drug Delivery Systems; Electrophoresis; Equipment Design; Polyelectrolytes
PubMed: 34194928
DOI: 10.1002/advs.202003995 -
The Yale Journal of Biology and Medicine Apr 1972
Topics: Acetylcholine; Central Nervous System; England; History, 20th Century; Neurophysiology; Nobel Prize; Parasympathetic Nervous System; Synapses; Synaptic Transmission
PubMed: 4336479
DOI: No ID Found -
The European Respiratory Journal Dec 2000The aim of the present study was to elucidate whether Chinese traditional herbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth muscle...
The aim of the present study was to elucidate whether Chinese traditional herbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth muscle tone and, if so, to determine what the mechanism of action is. Rabbit tracheal segments were isolated and the contractile responses to electrical field stimulation and acetylcholine were measured before and after the application of TJ-17 or TJ-23 under isometric conditions in vitro. Ouabain-sensitive rubidium-86 (86Rb) uptake by tissues in response to each drug was also measured. Each herbal medicine attenuated the contractile responses to electrical field stimulation and acetylcholine in a concentration-dependent manner, the maximal inhibition of acetylcholine-induced contraction being 37.5+/-4.9% for TJ-17 and 42.4+/-5.3% for TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of the epithelium, indomethacin, the nitric oxide synthase inhibitor NG -nitro-L-arginine methyl ester, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor adenosine 3'5'-cyclic monophosphorothioate (Rp-cAMPS), the cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor KT5823, or the calcium (Ca2+)-activated potassium (K+) channel inhibitor charybdotoxin, but were greatly inhibited in the presence of the sodium (Na+)-K+ adenosine triphosphatase (ATPase) inhibitor ouabain. Incubation of tissues with TJ-17 and TJ-23 dose dependently increased ouabain-sensitive 86Rb uptake. The results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce airway smooth muscle tone via a postjunctional mechanism probably through stimulation of the sodium pump and the subsequent hyperpolarization/repolarization of the cell membrane. These effects may contribute to the antiasthmatic properties of these herbal medicines.
Topics: Acetylcholine; Animals; Bronchial Provocation Tests; Bronchoconstriction; Culture Techniques; Drugs, Chinese Herbal; Female; Male; Medicine, Kampo; Muscle, Smooth; Rabbits
PubMed: 11292117
DOI: 10.1034/j.1399-3003.2000.16f18.x -
The Journal of General Physiology Feb 2002The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm...
The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10--500 nM acetylcholine (ACH) induced a contraction of the airway lumen and a transient increase in [Ca(2+)](i) in individual SMCs that subsequently declined to initiate multiple intracellular Ca(2+) oscillations. These Ca(2+) oscillations spread as Ca(2+) waves through the SMCs at approximately 48 microm/s. The magnitude of the airway contraction, the initial Ca(2+) transient, and the frequency of the subsequent Ca(2+) oscillations were all concentration-dependent. In a Ca(2+)-free solution, ACH induced a similar Ca(2+) response, except that the Ca(2+) oscillations ceased after 1--1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca(2+) signaling. A comparison of airway contraction with the ACH-induced Ca(2+) response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca(2+) transient, and that sustained airway contraction correlated with the occurrence of the Ca(2+) oscillations. Buffering intracellular Ca(2+) with BAPTA prohibited Ca(2+) signaling and airway contraction, indicating a Ca(2+)-dependent pathway. Cessation of the Ca(2+) oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca(2+) resulted in a relaxation of the airway. The concentration dependence of the airway contraction matched the concentration dependence of the increased frequency of the Ca(2+) oscillations. These results indicate that Ca(2+) oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca(2+) release from the SR involving IP(3)- and ryanodine receptors, and are required to maintain airway contraction.
Topics: Acetylcholine; Animals; Calcium Signaling; Dose-Response Relationship, Drug; In Vitro Techniques; Lung; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth
PubMed: 11815668
DOI: 10.1085/jgp.119.2.187 -
British Journal of Pharmacology Jun 19811 The effects of atropine, methylatropine and lachesine administered by ionophoresis were examined on responses of Renshaw cells to acetylcholine,...
1 The effects of atropine, methylatropine and lachesine administered by ionophoresis were examined on responses of Renshaw cells to acetylcholine, acetyl-beta-methylcholine, nicotine and DL-muscarine in cats anaesthetized with pentobarbitone or chloralose. 2 The antagonists were as effective in antagonizing excitation by nicotine as they were in antagonizing excitation by acetylcholine and were only slightly more effective in antagonizing excitation by acetyl-beta-methylcholine. 3 These results are discussed in relation to the characterization of acetylcholine receptors on Renshaw cells. 4 It is concluded that there are two distinct populations of receptors but that the nicotinic receptors are non-selective in their activation by agonists and antagonists, whereas the muscarinic receptors display greater selectivity.
Topics: Acetylcholine; Action Potentials; Animals; Atropine; Cats; Electric Stimulation; Interneurons; Nicotine; Receptors, Cholinergic; Receptors, Muscarinic; Spinal Cord
PubMed: 7236994
DOI: 10.1111/j.1476-5381.1981.tb10442.x