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At least 19 recordsLinked to original sources
PubMed1977

Postsynaptic membranes in the electric tissue of Narcine: IV. Isolation and characterization of the nicotinic receptor protein.

The nicotinic receptor protein of the electric tissue of Narcine was purified in several different media by partial isolation of postsynaptic membranes and affinity chromatography. Protease inhibitors were found to be necessary to prevent degradation of the protein, and both EDTA and Tris buffer were used in addition to prevent intramolecular crosslinking of 44,000 and 58,000 dalton subunits by tissue factors. The intact protein was found to have a molecular weight close to 400,000, and appears to be composed of four subunits of 44,000 daltons, two to three of 48,000, one of 58,000 and one of 65,000. All the subunits are glycoproteins and their amino acid compositions show similar hydrophobicity and acidity, suggesting similar positioning in postsynaptic membranes. Crosslinking experiments showed that acetylcholine and alpha-bungarotoxin bind to the smallest subunit, and suggest the juxtaposition of at least two of these subunits, and of all four toxin molecules bound to a receptor molecule. Morphological studies of the protein in membranes and after purification indicated cylindrial molecules with central cores.

Acetylcholine↗
PubMed1978

Distribution of an alpha-bungarotoxin-binding cholinergic nicotinic receptor in rat brain.

Cholinergic nicotinic receptors in rat brain were demonstrated by the use of the potent nicotinic antagonist [125I]alpha-bungarotoxin [125I]alpha-Btx). Biochemical studies on binding of [125I]alpha-Btx to rat hippocampal homogenates revealed saturable binding sites which are protected by nicotine, D-tuborcurarine and acetylcholine but not by atropine or oxotremorine. The hippocampus and hypothalamus displayed relatively high [125I]alpha-Btx specific binding whereas the cerebellum was devoid of specific binding. Other regions displayed intermediate binding levels. Analysis of the regional distribution of [125I]alpha-Btx binding by autoradiography of frontal brain sections revealed high labeling in the hippocampus, hypothalamic supraoptic, suprachiasmatic and periventricular nuclei, ventral lateral geniculate and the mesencephalic dorsal tegmental nucleus. It is suggested that the limbic forebrain and midbrain structures as well as sensory nuclei are the main nicotinic cholinoceptive structures in the brain.

Animals↗
PubMed1978

Blockade of desensitization of nicotinic receptors of the cat adrenal medulla by concanavalin A.

1 The possibility of concanavalin A (Con A) blocking the development of desensitization of nicotinic receptors of the cat adrenal gland has been investigated. 2 During perfusion of the adrenal gland with Krebs-bicarbonate solution containing acetylcholine (ACh), the rate of catecholamine (CA) secretion was very high in the first 2 min; thereafter, as perfusion with ACh was continued the output fell, to reach about 20% of the initial value in 10 minutes. When the adrenal gland was pretreated with Con A, the subsequent desensitization of release during continued infusion of ACh was prevented. 3 When the adrenal gland was perfused with high K+ solution, there was always a large initial secretion of CA, and as perfusion with high K+ continued the output fell, to reach about 15% of the initial rate in 10 minutes. Con A did not affect the rate of CA secretion induced by high K+. 4 It is tentatively suggested that Con A blocks the desensitization of CA secretion evoked by ACh by interaction with the glycoprotein moiety of the nicotinic receptor of adrenal chromaffin cells.

Acetylcholine↗
PubMed1978

Interaction of the acetylcholine (nicotinic) receptor protein from Torpedo marmorata electric organ with monolayers of pure lipids.

Membrane fragments rich in cholinergic (nicotinic) receptor protein were purified from the electric organ of Torpedo marmorata. Their lipid composition is essentially characterized by the prominence of cholesterol, phosphatidylethanolamine and phosphatidylcholine, long-chain fatty acyl constituents, and the absence of sphingomyelin. Solubilised receptor was purified from these fragments and the concentration of sodium cholate lowered by dialysis to 0.01% (w/v). When this preparation was injected under a lipid monolayer, an increase of surface pressure developed, which was not observed with the detergent alone nor in the absence of lipid film. When covalently radiolabelled receptor preparations were injected at a constant surface pressure the radioactivity recovered with the film was proportional to the increase in area. It is concluded that the pressure or area increases are due to the penetration of the cholinergic receptor protein into the lipid film. Incorporation experiments into films formed from various pure lipids showed that the protein interacts more readily with cholesterol than with ergosterol, phosphatidylcholine, or other phospholipids. Its affinity is also higher for long-chain phosphatidylcholines than for short-chain ones. The degree of unsaturation and fluidity of the 3-sn-phosphatidylcholine (lecithin) films are of secondary importance. Parallel experiments with covalently and non-covalently labelled receptor preparations showed that part of the protein recovered with the film lost its alpha-toxin binding ability during the penetration. Similar data were obtained with the receptor purified from Electrophorus electricus electric organ.

Animals↗
PubMed1978

Chick sympathetic neurons develop receptors for alpha-bungarotoxin in vitro, but the toxin does not block nicotinic receptors.

Studies were carried out on the development and physiological role of receptors for alpha-bungarotoxin (alphaBT) on chick embryo sympathetic neurons maintained in dissociated cell culture. Neurons from embryos of 13 days incubation (E13) developed alphaBT receptors in vitro with a time course and to a maximum level per cell similar to that previously observed for such neurons in vivo. In vitro receptor development by E11 and E8 neurons was also present, but (in comparison with E13 neurons) reached somewhat lower maximal levels. Receptor development in vitro was not affected by exclusion of non-neuronal cells from the cultures. In the present and in previous studies, binding of alphaBT to chick sympathetic neurons was blocked by a variety of ligands of nicotinic acetylcholine receptors. However, saturating concentrations of toxin were found here to be ineffective in blocking either (a) release of [3H]norepinephrine from the cultured neurons elicited via nicotinic stimulation of acetylcholine receptors or (b) depolarizing responses of the cultured neurons elicited by iontophoretically applied acetylcholine and nicotine. Kinetic studies further revealed that, while the idssociation of alphaBT from the cultured neurons is considerably enhanced in the presence of a cholinergic ligand (100 micrometer nicotine), the rate of this dissociation (t1/2 congruent to 30 min) appears to be too slow to account for the inability of the toxin to block nicotinic responses. Such findings show that chick embryo sympathetic neurons can develop receptors for alphaBT both in vivo and in vitro, but that the toxin does not block activation of their nicotinic acetylcholine receptors. The physiologic nature of specific binding sites for alphaBT on such neurons is thus presently unclear.

Acetylcholine↗
PubMed1977

Postsynaptic membranes in the electric tissue of Narcine: II. A freeze-fracture study of nicotinic receptor molecules.

The ventral, postsynaptic membranes of the electroplaques of Narcine were found to containe intramembranous particles similar in location, packing density (about 5700/micron 2), transmembrane position and end appearance to nicotinic acetylcholine receptor-channel molecules. In fixed tissue the particles were limited to the cytoplasmic lamina, while in unfixed tissue an equivalent number were found symmetrically in both laminae. Four populations of particle diameters were observed in each unfixed lamina, even though other morphological evidence indicates the presence of large number of molecules of uniform structure, and biochemical studies of isolated postsynaptic membranes indicate that at least 70% of the membrane protein is receptor-channel protein. Intramembranous particles in dorsal, non-innervated electroplaque membranes, presumably representing Na+, K+-associated ATPase and other channel proteins, were found to have similar characteristics to particles in ventral membranes. Receptor-channel molecules cannot, therefore, be distinguished from other intrinsic membrane proteins by freeze-replication alone.

Animals↗
PubMed1978

Properties of an alpha-bungarotoxin-binding cholinergic nicotinic receptor from Drosophila melanogaster.

alpha-[125I]Bungarotoxin specifically binds to homogenates of Drosophila melanogaster head at levels of 0.3-0.8 pmol/mg protein. The dissociation constant calculated from rates of association and dissociation of toxin.receptor complex, is 0.6.10(-9) M. Ca2+, and to a lesser extent Na+, inhibit the reaction. alpha-[125I]Bungarotoxin binding is inhibited by low concentrations of unlabelled toxin, nicotinic ligands and eserine, but not by low concentrations of muscarinic ligands, decamethonium or an organophosphate. The receptor is membrane bound and can be partially released into 100 000 X g supernatant by combination of 1 M NaCl and 1% Triton X-100. Most of the activity in the supernatant sediments after further centrifugation at 200 000 X g for 2 h. Toxin binding sites are distinct from acetylcholinesterase molecules as revealed by pharmacological, biochemical and genetic techniques. The gene for the toxin-binding nicotinic receptor in Drosophila is apparently not located adjacent to the gene for acetylcholinesterase.

Acetylcholinesterase↗
PubMed1977

Prevention by drugs of tachyphylaxis at nicotinic receptors in the cat superior cervical ganglion in situ.

A new compound, AF3 (4-ethyl-6-oxa-1-azatricyclo)4.2.2.02,7)dodecan-5-one), and its 4-phenyl analogue, AF6, embodying the structural elements of acetylcholine in a highly rigid framework, were shown to evoke nicotine-like responses in the nictitating membrane (NM) and blood pressure when applied to the superior cervical ganglion in anaesthetized cats. In this respect, their equiactive molar ratio was (nicotine : 1),20-30. However, at doses that were too low to evoke any response, AF3 appeared to potentiate the responses to nicotine or tetra-methylammonium (TMA) by preventing or abolishing tachyphylaxis to the two latter drugs, the effect being dose-dependent with AF3. DMPP which produces much less tachyphylaxis, or preganglionic nerve stimulation, was little or not potentiated in presence of AF3. It is proposed that potentiation to nicotine or TMA occurs following occupancy by AF3 of a regulatory subsite, thereby preventing further access to it by nicotine or TMA. In this respect, AF3 plays the role of a "neutral" molecule.

Animals↗
PubMed1977

Possibilities for a cholinergic action on smooth musculature and on sympathetic axons in brain vessels mediated by muscarinic and nicotinic receptors.

A pharmacological identification and characterization of cholinergic receptors was carried out in pial arteries of cats. In one series of experiments, the middle cerebral artery was suspended in an organ bath for recording fo circular motor activity. Parasympathomimetic compounds produced either a relaxation or a contraction. The relaxation occurred at low doses (up to 10(-6) M), and the response was inhibited in a competitive manner by atropine. The mean KB value (determined with acetylcholine as agonist) was 3.85 X 10(-11) M, and the corresponding pA2 value 10.43. At higher doses, the parasympathomimetics produced a contraction. This effect, too, was inhibited in a competitive manner with atropine. The calculated mean KB value with acetylcholine as agonist was 1.12 X 10(-11) M, and pA2 was 10.07. The motor responses did not require an intact perivascular sympathetic innervation, which shows that the effects were mediated by muscarinic type of cholinergic receptors present in the smooth musculature. In another series of experiments, pial arteries were preincubated in the presence of 3H-norepinephrine, and the amount of tritium efflux was measured in a superfusion system before or during electrical field stimulation (12 V, 1 msec pulse duration, 10 Hz). The efflux was minimized by sympathetic denervation, and the effect of transmural stimulation abolished by bretylium and guanethidine, which shows that the bulk of tritium overflow during stimulation originated from the perivascular sympathetic nerves. The marked elevation of tritium efflux during stimulation was enhanced by hexamethonium, and it was inhibited by nicotine and acetylcholine, whose effects were counteracted by hexamethonium (but not by atropine). This finding indicates the presence of nicotinic type of cholinergic receptors on the perivascular adrenergic nerves, allowing inhibition of norepinephrine by acetylcholine that may be liberated from the adjacent cholinergic terminals in the autonomic nerve plexus.

Acetylcholine↗