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Biology Letters May 2018Vestigial morphological traits are common and well known in a variety of taxa. Identification of vestigial genes has illustrated the potential for evolutionary reversals...
Vestigial morphological traits are common and well known in a variety of taxa. Identification of vestigial genes has illustrated the potential for evolutionary reversals and the re-expression of atavistic traits. Here we induce expression of a behavioural sexual signal, male calling song, in a cricket species, which lacks a functional calling song. We successfully used acetylcholine injections in the frontal space of the head of male crickets to activate cerebral command neurons for cricket calling, and we recorded calling songs with a temporal chirp pattern similar to that of ' close evolutionary relatives, and , implying that the neural pattern generators that underlie cricket calling behaviour persist in a vestigial state in To our knowledge, this is the first demonstration of the induced expression of a vestigial behaviour in any organism. The retention of latent neural capacity to express sexual behaviours could have important implications for rapid evolution, trait re-emergence and reproductive isolation.
Topics: Acetylcholine; Animals; Gryllidae; Male; Sexual Behavior; Vocalization, Animal
PubMed: 29769298
DOI: 10.1098/rsbl.2018.0095 -
BMC Structural Biology 2002Nicotine is a psychoactive drug presenting a diverse array of biological activities, some positive, such as enhancement of cognitive performances, others negative, such...
BACKGROUND
Nicotine is a psychoactive drug presenting a diverse array of biological activities, some positive, such as enhancement of cognitive performances, others negative, such as addiction liability. Ligands that discriminate between the different isotypes of nicotinic acetylcholine receptors (nAChRs) could present improved pharmacology and toxicity profile.
RESULTS
Based on the recent crystal structure of a soluble acetylcholine binding protein from snails, we have built atomic models of acetylcholine and nicotine bound to the pocket of four different human nAChR subtypes. The structures of the docked ligands correlate with available biochemical data, and reveal that the determinants for isotype selectivity are relying essentially on four residues, providing diversity of the ligand binding pocket both in terms of Van der Waals boundary, and electrostatic potential. We used our models to screen in silico a large compound database and identify a new ligand candidate that could display subtype selectivity.
CONCLUSION
The nAChR-agonist models should be useful for the design of nAChR agonists with diverse specificity profiles.
Topics: Acetylcholine; Amino Acid Sequence; Binding Sites; Humans; Ligands; Models, Molecular; Molecular Sequence Data; Nicotine; Protein Isoforms; Protein Subunits; Receptors, Nicotinic; Sequence Alignment
PubMed: 11860617
DOI: 10.1186/1472-6807-2-1 -
Scientific Reports Apr 2022Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions...
Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose-response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.
Topics: Acetylcholine; Humans; Iontophoresis; Skin; Spectrum Analysis; Vasodilation
PubMed: 35449189
DOI: 10.1038/s41598-022-10617-x -
Japanese Journal of Pharmacology Jun 1972
Topics: Acetates; Acetylcholine; Animals; Anura; Biological Assay; Chickens; Female; Intestine, Small; Methods; Trichloroacetic Acid
PubMed: 4539400
DOI: 10.1254/jjp.22.425 -
Biomolecules Jun 2022Perivascular adipose tissue (PVAT) enhances vascular relaxation of mesenteric arteries in SHRSP.Z-/IzmDmcr rats (SPZF), a metabolic syndrome model. We investigated and...
Modulation of Vasomotor Function by Perivascular Adipose Tissue of Renal Artery Depends on Severity of Arterial Dysfunction to Nitric Oxide and Severity of Metabolic Parameters.
Perivascular adipose tissue (PVAT) enhances vascular relaxation of mesenteric arteries in SHRSP.Z-/IzmDmcr rats (SPZF), a metabolic syndrome model. We investigated and compared the effects of PVAT on the renal artery in SPZF with those on SHR/NDmcr-cp rats (CP). Renal arteries with and without PVAT were isolated from 23-week-old SPZF and CP. The effects of PVAT on acetylcholine- and nitroprusside-induced relaxation were examined using bioassays with phenylephrine-contracted arterial rings. Acetylcholine-induced relaxations without PVAT in SPZF and CP were 0.7- and 0.5-times lower in females than in males, respectively. In the presence of PVAT, acetylcholine-induced relaxations increased 1.4- and 2-times in male and female CP, respectively, but did not differ in SPZF. Nitroprusside-induced relaxation with and without PVAT was 0.7-times lower in female than in male SPZF but did not differ in CP. Angiotensin-II type-1 receptor (AT1R)/AT1R-associated protein mRNA ratios were lower in CP than in the SPZF and negatively correlated with the difference in arterial relaxation with and without PVAT. The effects of renal artery PVAT differed between the SPZF and CP groups. Higher levels of enhanced AT1R activity in SPZF PVAT may drive these differences by impairing the vascular smooth muscle responses to nitric oxide.
Topics: Acetylcholine; Adipose Tissue; Animals; Female; Male; Nitric Oxide; Nitroprusside; Rats; Rats, Inbred SHR; Receptor, Angiotensin, Type 1; Renal Artery; Vasodilation
PubMed: 35883426
DOI: 10.3390/biom12070870 -
The Journal of Physiology Sep 19701. Acetylcholine and neurohypophysial hormones were measured in subcellular fractions of rabbit neurohypophysis.2. Differential and density gradient centrifugation,...
1. Acetylcholine and neurohypophysial hormones were measured in subcellular fractions of rabbit neurohypophysis.2. Differential and density gradient centrifugation, followed by bio-assay and electron microscopy were used to separate and characterize the subcellular particles, or isolated nerve endings.3. Acetylcholine in the rabbit neurohypophysis was found to occur in small vesicles of about 40 nm diameter which had similar characteristics to the synaptic vesicles from central nervous tissue.4. Examination of intact nerve endings isolated from the rabbit neurohypophysis indicated that at least some acetylcholine and neurohypophysial hormones occurred in separate nerve endings.
Topics: Acetylcholine; Animals; Centrifugation, Density Gradient
PubMed: 5500778
DOI: 10.1113/jphysiol.1970.sp009203 -
British Journal of Clinical Pharmacology Apr 1997Transdermal iontophoresis in combination with laser Doppler fluxmetry (LDF) are useful techniques for examining dermal microcirculatory responses to different... (Clinical Trial)
Clinical Trial
AIMS
Transdermal iontophoresis in combination with laser Doppler fluxmetry (LDF) are useful techniques for examining dermal microcirculatory responses to different vasodilators. Differences in skin and microcirculation structure could influence the recorded baseline flux, and the observed vasodilatation. To examine this we compared baseline flux and the response of microvascular blood flow to a single vasodilator, acetylcholine, at sites in the forearm and hand.
METHODS
Baseline microcirculation flow was recorded by LDF in a temperature controlled laboratory. The change in flux with iontophoresis of identical doses of acetylcholine, 150 microA for 40 s, was recorded at 12 different sites in the forearm and hand in 10 female and 3 male subjects.
RESULTS
Baseline flux patterns and the vasodilatation to identical periods of iontophoresis of acetylcholine were site dependent. Palmar sites showed a higher baseline flux, but no vasodilatation to iontophoresis of acetylcholine. In contrast the volar forearm, dorsal hand and finger sites showed lower site-dependent baseline flux, but did vasodilate.
CONCLUSIONS
Patterns of baseline flux are specific to sites on the hand and forearm reflecting differences in underlying microvascular structure. The vasodilatation to transdermal delivery of acetylcholine is also site dependent, but differences in skin structure may be more important than the underlying microvasculature in determining the response.
Topics: Acetylcholine; Administration, Cutaneous; Adult; Female; Forearm; Hand; Humans; Iontophoresis; Laser-Doppler Flowmetry; Male; Regional Blood Flow; Skin; Vasodilation
PubMed: 9146851
DOI: 10.1046/j.1365-2125.1997.00558.x -
The Journal of Physiology Feb 19871. The balance between acetylcholine (ACh) synthesis and degradation and the availability of choline were studied in the neuromuscular junction of rats aged 10 (mature...
1. The balance between acetylcholine (ACh) synthesis and degradation and the availability of choline were studied in the neuromuscular junction of rats aged 10 (mature adult) and 28 (aged) months. Endogenous and 2H4-labelled variants of ACh and choline were assayed during steady-state stimulated and resting conditions using gas chromatography-mass spectrometry. 2. Endogenous ACh levels were 34% less per nerve terminal in the older rats; in non-innervated tissue, the levels were 12-14% as large as in innervated tissue. Endogenous choline levels in innervated and non-innervated tissue were similar and were 28% higher in the older animals. 3. Accumulation of 2H4-labelled choline was significantly greater in the 28-month animals; the specific activity at equilibrium was 60% higher in the older rats. 4. Incorporation of [2H4]choline into [2H4]ACh was significantly faster in the aged rats; times to half-maximal values were 2.0 and 0.6 min in the 10- and the 28-month animals, respectively. There was no measurable synthesis of ACh in the non-innervated tissue. 5. There were no major age-related differences in the amount of ACh released during stimulation between 1 and 20 Hz. In contrast, choline efflux during stimulation was significantly greater in the aged animals; flux values (+/- S.E. of mean) were 0.48 (+/- 0.014) and 0.66 (+/- 0.038) nmol/min for the 10- and the 28-month rats, respectively. 6. Under resting conditions, endogenous ACh efflux was significantly greater in the older rats; the rates (+/- S.E. of mean) were 2.00 (+/- 0.21) and 3.05 (+/- 0.43) pmol/min for the younger and the older animals, respectively; similarly, choline efflux was greater in the aged tissue. 7. These results indicated that lower intracellular ACh levels can be attributed to enhanced leakage rather than to decreased synthesis. Greater ACh efflux is accompanied by correspondingly greater choline uptake in the 28-month rats; this is associated with greater choline efflux and higher steady-state choline levels in the aged tissue.
Topics: Acetylcholine; Aging; Animals; Choline; Electric Stimulation; Neuromuscular Junction; Rats; Rats, Inbred F344; Time Factors
PubMed: 3656139
DOI: 10.1113/jphysiol.1987.sp016436 -
Neuropharmacology Oct 2019α6-containing (α6*) nicotinic acetylcholine receptors (nAChRs) are expressed throughout the periphery and the central nervous system and constitute putative...
α6-containing (α6*) nicotinic acetylcholine receptors (nAChRs) are expressed throughout the periphery and the central nervous system and constitute putative therapeutic targets in pain, addiction and movement disorders. The α6β2* nAChRs are relatively well studied, in part due to the availability of target specific α-conotoxins (α-Ctxs). In contrast, all native α-Ctxs identified that potently block α6β4 nAChRs exhibit higher potencies for the closely related α6β2β3 and/or α3β4 subtypes. In this study, we have identified a novel peptide from Conus ventricosus with pronounced selectivity for the α6β4 nAChR. The peptide-encoding gene was cloned from genomic DNA and the predicted mature peptide, α-Ctx VnIB, was synthesized. The functional properties of VnIB were characterized at rat and human nAChRs expressed in Xenopus oocytes by two-electrode voltage clamp electrophysiology. VnIB potently inhibited ACh-evoked currents at rα6β4 and rα6/α3β4 nAChRs, displayed ∼20-fold and ∼250-fold lower potencies at rα3β4 and rα6/α3β2β3 receptors, respectively, and exhibited negligible effects at eight other nAChR subtypes. Interestingly, even higher degrees of selectivity were observed for hα6/α3β4 over hα6/α3β2β3 and hα3β4 receptors. Finally, VnIB displayed fast binding kinetics at rα6/α3β4 (on-rate t = 0.87 min, off-rate t = 2.7 min). The overall preference of VnIB for β4* over β2* nAChRs is similar to the selectivity profiles of other 4/6 α-Ctxs. However, in contrast to previously identified native α-Ctxs targeting α6* nAChRs, VnIB displays pronounced selectivity for α6β4 nAChRs over both α3β4 and α6β2β3 receptors. VnIB thus represents a novel molecular probe for elucidating the physiological role and therapeutic properties of α6β4* nAChRs.
Topics: Acetylcholine; Animals; Conotoxins; Conus Snail; Dose-Response Relationship, Drug; Humans; Kinetics; Nicotinic Antagonists; Oocytes; Patch-Clamp Techniques; Rats; Receptors, Nicotinic; Xenopus laevis
PubMed: 31255696
DOI: 10.1016/j.neuropharm.2019.107691 -
Anaesthesia Jul 1969
Review
Topics: Acetylcholine; Action Potentials; Animals; Cats; Cell Membrane; Choline; Humans; Membrane Potentials; Muscles; Myasthenia Gravis; Neoplasms; Neuromuscular Junction; Rats; Receptors, Drug; Succinylcholine; Tetraethylammonium Compounds
PubMed: 4892960
DOI: 10.1111/j.1365-2044.1969.tb02878.x