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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 217 records · Page 12Linked to original sources
PubMed1975

Effects of potassium chloride and smooth muscle relaxants on tension and cyclic nucleotide levels in rat myometrium.

Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP) were decreased by 40%. At this point both nitroglycerin (4 X 10(-4) M) and papaverine (2 X 10(-5) M) were capable of relaxing the depolarized muscles without significantly increasing cyclic AMP levels. Isoproterenol, in concentrations from 5 X 10(-9) M to 10(-6) M, relaxed the depolarized muscles and significantly increased tissue levels of cyclic AMP. However, the magnitudes of the cyclic AMP increases seen after the lower concentrations of isoproterenol were small relative to the increases observed during KCl-contracture alone. For example, the 40% elevation of cyclic AMP seen 10 min after KCl-depolarization did not cause the muscles to relax, whereas 5 X 10(-9) M isoproterenol caused relaxation with an increase in cyclic AMP levels of only 16% over depolarized controls. It was concluded that changes in total tissue levels of cyclic AMP were not responsible for the uterine relaxation caused by nitroglycerin, papaverine or isoproterenol in these experiments. Cyclic GMP levels in the depolarized muscles were not significantly changed by isoproterenol or papaverine but were increased approximately 80% by nitroglycerin. The above results are not consistent with the previously suggested roles for cyclic GMP and cyclic AMP as mediators of smooth muscle contraction and relaxation, respectively.

Animals↗
PubMed1973

The membrane effects, and sensitivity to strychnine, of neural inhibition of the Mauthner cell, and its inhibition by glycine and GABA.

1. Anionic conductance changes in Mauthner neurones of goldfish were measured during synaptically evoked inhibition and inhibition caused by iontophoretic application of the putative inhibitory transmitters glycine and gamma-aminobutyric acid (GABA).2. The effects of either amino acid were indistinguishable from those of the neural inhibitory transmitter(s). The membrane permeability during the neural or drug response was increased to Br(-), Cl(-), I(-), SCN(-), NO(3) (-), ClO(3) (-), and formate (HCOO(-)), but not to HCO(3) (-), BrO(3) (-), IO(3) (-), SO(4) (-), HPO(4) (-), H(2)PO(4) (-), acetate and citrate.3. Strychnine was injected intramuscularly, iontophoretically, or applied topically to the exposed brain in order to compare quantitatively its ability to prevent inhibition evoked by synaptic activation and by pharmacological means. Inhibitions were measured by the increase in membrane conductance.4. Strychnine, at concentrations just adequate to block completely the late collateral inhibition (LCI) and crossed VIII nerve inhibition, had little effect on the pharmacological inhibition caused by glycine, and sometimes there was no detectable effect at all. In one experiment even a local iontophoretic application of strychnine in a sufficient dose to diffuse over the cell and block the LCI almost completely, merely halved the effect of a small dose of glycine applied to the same localized region of the membrane.5. Higher concentrations of strychnine than those necessary to block synaptically evoked inhibition would reduce the effect of glycine but not that of GABA. The evidence indicated that any apparent effect of strychnine upon GABA could be explained by displacement of the GABA-containing iontophoretic pipette.6. The glycine-blocking action of iontophoretic pulses of strychnine was of relatively very slow onset and long duration compared to the effects of pulses of glycine and GABA.7. These findings can be interpreted as either (1) strychnine has a presynaptic action, preventing the release of inhibitory neurotransmitter, in addition to its less potent post-synaptic one in blocking pharmacological inhibition, or (2) strychnine acts entirely post-synaptically, but the physiological transmitter action differs from that of glycine and GABA in being considerably more sensitive to strychnine antagonism. In either case, the use of strychnine as evidence for the claim that glycine is an inhibitory neurotransmitter at the Mauthner cell is questionable.

Aminobutyrates↗
PubMed1973

Analysis of Mauthner cell responses to iontophoretically delivered pulses of GABA, glycine and L-glutamate.

1. The intracellularly recorded responses of goldfish Mauthner neurones to iontophoretically applied pulses of amino acids have been analysed: their time courses have been compared with each other, and with those predicted from diffusion theory.2. The rise time of the response to GABA is slower than that to glycine or L-glutamate. The response curves of the latter substances were very similar, and unlike that of GABA were markedly affected by increasing the distance of pipette-tip from the membrane. The results suggest that the time course of the responses to glycine and L-glutamate are determined mainly by free diffusion in the brain tissue (at least within about 200 mum of the cell), while that to GABA must be rate-limited by other factors, e.g. drug-receptor activation time.3. The possibility that the responses are influenced by some desensitizing process was investigated by applying a second (test) drug pulse during the response to a prior conditioning one. In the case of glycine and of L-glutamate there was no attenuation of the response to a second pulse at any time. With GABA, however, the second response was reduced during the period of the conditioning response; the reduction was progressively less marked the later the test pulse occurred. A similar effect with GABA was seen when glycine was used as the test pulse. The responses to long-maintained drug pulses also indicated that for GABA, but not for glycine or glutamate, there seems to be some desensitizing process present.4. Calculated time courses of responses to brief pulses of glycine and of L-glutamate (based upon diffusion theory) differed somewhat from the observed curves, largely during the falling phase. However, when the calculations were based upon second-order reactions (two molecules of drug per receptor) the diffusion model gave results very like the observed ones.5. Possible implications of these results for the role these three amino acids may have as neuro-transmitters are mentioned.

Aminobutyrates↗
PubMed1973

Evidence that axoplasmic transport of trophic factors is involved in the regulation of peripheral nerve fields in salamanders.

1. We have compared the effects of partial denervation with those of colchicine-induced block of axoplasmic flow, on the peripheral fields of nerves innervating the hind limb of salamanders.2. Acute application of colchicine solution (0.03-0.10 M) to spinal nerve 16 results in a dose-dependent increase in skin and muscle fields of the adjacent nerves (15 and 17). The time course, magnitude and distribution of the response to 0.10 M colchicine is not distinguishable from that of the compensatory sprouting of nerves 15 and 17 that occurs after section of nerve 16.3. In contrast to the situation with nerve section, sprouting of adjacent nerves occurred after colchicine applications which produced no behavioural deficit, no change in the peripheral field of the treated nerve, and no interference with impulse conduction in it; nor was there subsequent degeneration in the nerve.4. The same concentrations of colchicine reduced the axoplasmic flow of catecholamines and cholinesterase; treated nerves contained fewer microtubules than untreated controls.5. A similar application of colchicine solution to nerve 15 prevented it from sprouting in response to the stimulus provided by section of nerve 16.6. We conclude that nerve terminals are continuously supplied by axoplasmic flow with a trophic factor concerned with the regulation of nerve fields. When the supply of this factor is reduced, adjacent nerves sprout and invade the territory of the treated nerve. In addition, the ability of nerves to sprout is itself dependent upon the maintenance of axoplasmic flow.

Action Potentials↗
PubMed1971

The effect of tetanus toxin in the goldfish.

1. The effects of tetanus toxin have been investigated both on central nervous and peripheral neuromuscular systems of goldfish.2. Tetanus toxin kills goldfish when administered in minute doses. The lethal effect is temperature dependent. Unlike mammals, in which tetanus toxin produces spastic paralysis and convulsions, the tetanus-intoxicated goldfish die with an apparently flaccid paralysis.3. Inhibition and excitation were investigated on the Mauthner cells of goldfish which had been paralysed with tetanus toxin for at least 24 hr, and which were subsequently kept alive for up to 3 days by perfusing the gills with oxygenated water. In such fish, antidromically and orthodromically excited Mauthner cells were quite normal, and there was no apparent effect on either the collateral inhibition or the crossed VIIIth nerve inhibition.4. Local injection of sublethal doses of tetanus toxin into the pectoral fin muscles produced local paralysis of the fin. Nerve-muscle preparations were isolated from such goldfish; in tetanus toxin-paralysed fins, the muscle no longer responded to stimulation of its nerve. The nerve compound action potential was still present and the muscle still responded vigorously to direct electrical stimulation.5. It is concluded that the major part of the lethal action of the toxin in the fish must be ascribed to a peripheral effect, the blocking of neuromuscular transmission. The inhibitory neuronal systems acting on the Mauthner cells of the goldfish, in apparent contrast to those acting on mammalian spinal neurones, are highly insensitive to tetanus toxin.

Action Potentials↗