Sulfur and selenium isologs related to acetylcholine and choline IV. Activity in the electroplax preparation

Mautner, Henry G.; Bartels, Eva; Webb, G. A.

doi:10.1016/0006-2952(66)90059-1

Cited by 46 publications

(18 citation statements)

References 19 publications

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“…Perhaps the best evidenbe that the nicotine-binding fraction has specificity for binding cholinergic molecules is the striking inactivity of choline, a cotnkound that is a very poor agonist in the eel electroplax (33) and which, even after venom treatment, has little or no effect on the action potential of intact squid axons (32). In addition, the inhibitory effects of all the cholinergic ligands tested on [3H]nicotine binding (Table 3) are compatible with the hypothesis that a cholinergic binding macromolecule can be identified in axon plasma membranes (16).…”

Section: Resultsmentioning

confidence: 99%

Interaction of cholinergic ligands and local anesthetics with plasma membrane fragments from lobster axon.

Marquis¹,

Hilt²,

Papadeas³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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ABSIRACr Isologous local anesthetics containing the ester, thiolester, or selenolester grouping and their quaternary ammonium analogs were studied for their ability to displace[3H]nicotine from plasma membrane fragments of lobster nerve.Tertiary and quaternary analogs were equiactive. The relative ability of oxo, thio, and selenGo analogs to displace nicotine was the same as their relative ability to block axonal conduction and synaptic transmission. Among cholinergic ligands, choline and aminocholine, previously shown to be inactive as depolarizing agents, were uniquely unable to displace nicotine. The findings are compatible with the presence of a biopolymer capable of binding cholinergic ligands in axonal membranes and support the postulate that the relative inactivity of quaternary compounds in intact axons is due to permeability barriers.

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Section: Resultsmentioning

confidence: 99%

Interaction of cholinergic ligands and local anesthetics with plasma membrane fragments from lobster axon.

Marquis¹,

Hilt²,

Papadeas³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…If ACh moved in the cleft by free diffusion (Do 10-5 cm2/sec-1; Fatt, 1954;Eccles & Jaeger, 1958;Krnjevic &Mitchell, 1960, andDryer & it would spread over the critical area of 03 #,m2 in < 15 ,usec. However, as suggested by Gage & McBurney (1975) Kd values are generally given as < 4 x 10-6 M (Mautner, Bartels & Webb, 1966;Dolly & Barnard, 1974;Meunier, Sealock, Olsen & Changeux, 1974;Moreau & Changeux, 1976). However, values as high as 2-3 x 10-5 M (Sheridan & Lester, 1975, corrected for -80 mV; Dreyer & Peper, 1975) have been reported.…”

Section: Discussionmentioning

confidence: 96%

Distribution of acetylcholine receptors at frog neuromuscular junctions with a discussion of some physiological implications.

Matthews-Bellinger¹,

Salpeter²

1978

The Journal of Physiology

215

124

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SUMMARY1. The distribution of acetylcholine receptors (AChR) at frog cutaneous pectoris neuromuscular junctions was studied quantitatively using [125I]a-bungarotoxin (a-BTX) labelling and EM autoradiography.2. We found that, as in mouse end-plates, the AChR is localized uniformly along the thickened post-junctional membrane. In the frog muscle this specialized membrane constitutes approximately the top 50 % of the junctional folds.3. The receptor site density is 26,000 + 6000 sites/,um2 on the thickened postjunctional membrane and falls sharply to 50 sites/fum2 within 15 Itm from the axon terminal.4. a-BTX site density on the presynaptic axonal membrane was directly determined to be at most 5 % of the value on the thickened post-junctional membrane.5. The high post junctional AChR site density leads us to conclude that: (a) each quantum of ACh needs to spread only over a very small post-junctional area (to be called the 'critical area') before it encounters as many AChR (plus AChE) sites as there are ACh molecules in the quantum (for a packet of 104 ACh molecules this critical area is-03 #um2), (b) the average concentration of ACh prevailing in

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“…Sulfur and selenium analogues of ACh and choline have been further studied by Mautner and colleagues (43)(44)(45). In the eserinized electrTplax preparation, depolarizing activity is progressively reduced as the ester-link ing oxygen of ACh is replaced by sulfur and selenium.…”

Section: Pharmacological and Biochemical Characteristicsmentioning

confidence: 97%

“…The hypothesis suffers from complexities resulting from efforts to explain apparent exceptions. Acetylcholine, acetylthiocholine and acetylselenocholine are reported to be hydrolyzed at similar rates but have markedly different depolarizing activities (45). Structural features permit ting esterase hydrolysis seem less critical than those for cholinergic site bind ing (94).…”

Section: Oxotremorine Arecolinementioning

confidence: 98%

“…A number of bis-nitrobenzyldimethylammonium ana logues of hexamethonium showed ganglionic blocking properties which varied inversely with neuromuscular blocking activities (59). Choline disul fides and diselenides were slightly more active than hexamethonium as anti depolarizing agents on the electroplax preparation (45). Some additional sterically hindered methylpiperidines have been evaluated as ganglionic blocking agents (60).…”

Section: Oxotremorine Arecolinementioning

confidence: 99%

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Some Relationships Between Chemical Structure and Pharmacological Activities

Cavallito¹

1968

Annu. Rev. Pharmacol.

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Earlier reviews in this series dealt with some relationships of chemical structure with biological activities (1-3) i the present assignment is restricted essentially to pharmacologically active compounds. As with the earlier re views, the published literature is not covered exhaustively, but some new re ports and observations are included which appeared from about September, 1964 [termination of coverage of last review (1)] to May, 1967. Where useful for purposes of relationship, selected older literature is cited.Over the years attempts have been made to devise general hypotheses pertaining to structure-activity relationships (SAR) and drug mechanisms of action. Recent efforts include variations of receptor occupancy hypotheses (Ariens, Stephenson), rate or kinetic hypotheses (Paton), and more chemi cally descriptive concepts (Belleau and others). In reviewing publications of the past two years that could be considered pertinent to SAR, one is im pressed by the gulf that exists between most synthesizers of new molecules and the developers of general hypotheses. For example, from 310 complete articles published in J. Med. Chern. (1965-66), only six made reference to these hypotheses either as stimuli for the project or as vehicles for cor relating SAR. This might indicate that the hypotheses are sterile or inade quate for either predictive or correlative purposes or that there is little in terest or inclination among most investigators in relating specific observa tions to general hypotheses. Most of these hypothes,t!s have indeed offered little that is of substantive value from a chemical perspective of devising novel molecules of biological interest. However, the efforts are commendable and some of these hypotheses may evolve and develop into theories with use ful correlative and predictive values. As hypotheses become more chemically descriptive, one can anticipate that there will be a greater consideration of such hypotheses by the designers of new, biologically interesting molecules.Their more recent concepts have been summarized by Ariens (4) and Paton (5). Shortcomings of the Ariens and Stephenson receptor occupancy and the Paton rate hypotheses have been analyzed by Belleau (6) as back ground for discussion of his "conformational perturbation" hypothesis.Bloom & Goldman (7) further consider these and modify and extend some of Belleau's views in proposing a "dynamic receptor hypothesis" relevant to catecholamine-adenine mononucleotide interactions in adrenergic mech anisms. These reviews are recommended to the cautious reader; space does 39 Annu. Rev. Pharmacol. 1968.8:39-66. Downloaded from www.annualreviews.org Access provided by New York University -Bobst Library on 05/14/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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Sulfur and selenium isologs related to acetylcholine and choline IV. Activity in the electroplax preparation

Cited by 46 publications

References 19 publications

Interaction of cholinergic ligands and local anesthetics with plasma membrane fragments from lobster axon.

Interaction of cholinergic ligands and local anesthetics with plasma membrane fragments from lobster axon.

Distribution of acetylcholine receptors at frog neuromuscular junctions with a discussion of some physiological implications.

Some Relationships Between Chemical Structure and Pharmacological Activities

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