Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined two sets of genes expressed early in the developmental cycle of Dictyostelium discoideum that appear to be regulated by cyclic AMP (cAMP). The transcripts of both sets of genes were not detectable in vegetative cells. During normal development on filter pads, RNA complementary to these genes could be detected at about 2 h, peaked around 6 to 8 h, and decreased gradually thereafter. Expression of these genes upon starvation in shaking culture was stimulated by pulsing the cells with nanomolar levels of cAMP, a condition that mimics the in vivo pulsing during normal aggregation. Expression was inhibited by caffeine or by continuous levels of cAMP, a condition found later in development when in vivo expression of these genes decreased. The inhibition of caffeine could be overcome by pulsing cells with cAMP. These results suggest that the expression is mediated via the cell surface cAMP receptor, but does not require a rise in intracellular cAMP. mRNA from a gene of the second class was induced upon starvation, peaked by 2.5 h of development, and then declined. In contrast to the other genes, its expression was maintained by continuous levels of cAMP and repressed by cAMP pulses. These and other results on a number of classes of developmentally regulated genes indicates that changing levels of cAMP, acting via the cell surface cAMP receptor, are involved in controlling these groups of genes. We also examined the structure and partial sequence of the cAMP pulse-induced genes. The two tandemly duplicated M3 genes were almost continuously homologous over the sequenced portion of the protein-coding region except for a region near the N-terminal end. The two M3 genes had regions of homology in the 5' flanking sequence and showed slight homology to the same regions in gene D2, another cAMP pulse-induced gene. D2 showed extremely significant homology over its entire sequenced length to an acetylcholinesterase. The results presented here and by others suggest that expression of many early genes in D. discoideum is regulated via the cell surface cAMP receptor. We expect that many of these genes may play essential roles in early Dictyostelium development and could code for elements of the cAMP signal transduction pathway involved in aggregation.
 ...
PMID:Cyclic AMP regulation of early gene expression in Dictyostelium discoideum: mediation via the cell surface cyclic AMP receptor. 303 75

The spinal cord is capable of initiating a significant and long-lasting pressor response following intrathecal injection of cholinergic agonists in freely moving rats. The magnitude of the pressor response to the cholinesterase inhibitor, neostigmine, was greatest when the site of injection was restricted to the thoracic level. Intrathecal (i.t.) injection of neostigmine (1-10 micrograms) elicited a dose-related increase in mean arterial pressure of up to 45 mm Hg which remained elevated for almost 2 h. Significant inhibition of acetylcholinesterase was localized to the spinal cord, with the thoracic region exhibiting the greatest degree of inhibition. Also, depletion of spinal acetylcholine levels following i.t. injection of hemicholinium-3 (HC-3) resulted in a significant reduction in the magnitude of the neostigmine-induced pressor response. Carbachol, a direct-acting cholinergic receptor agonist also increased mean arterial pressure following i.t. injection. However, the pressor response to carbachol was not reduced following HC-3. For both agonists, cardiovascular changes were accompanied by significant behavioral changes characterized by tremor, scratching, tail biting and chewing. The appearances of these behaviors following neostigmine injection were reduced in frequency and intensity in HC-3-pretreated animals. These findings demonstrate the ability of spinal cholinergic neurons to mediate a significant hypertensive response. The presence of marked behavioral changes accompanying the cardiovascular response suggests the possibility that cholinergic neurons may be part of an ascending spinal system.
 ...
PMID:Hypertension following intrathecal injection of cholinergic agonists in conscious rats: role of endogenous acetylcholine. 322 83

Tri-o-cresyl phosphate (TOCP), which produces a delayed neurotoxic syndrome in humans and some animal species, was given to Fischer 344 (F344) male (18 week old) rats to determine if it causes biochemical, sensorimotor, and neuropathological effects. Animals were given TOCP by gavage in doses ranging from 10 to 100 mg of TOCP/kg daily for a period of 63 days. The rats were subjected to a series of neurobehavioral tests including fore- and hindlimb grip strength, motor activity, tremor, and latency to respond to a thermal stimulus. Central and peripheral nervous tissues were examined for damage characteristic of organophosphorous compound-induced delayed neurotoxicity (OPIDN). Brain neurotoxic esterase and acetylcholinesterase activities were inhibited in a dose-dependent fashion. A group of three chickens treated with 100 mg of TOCP/kg/day for 18 days was included as the positive control for enzymatic and histopathological alterations associated with OPIDN. Rats showed no consistent neurobehavioral changes or evidence of neuropathological damage in nervous tissues associated with treatment. In contrast, chickens treated with TOCP developed delayed neurotoxicity characterized by ataxia, which progressed to paralysis. These neurological changes included swelling, fragmentation, and degeneration of the axon and myelin in both central and peripheral nervous tissues. This study concludes that the F344 rat is not sensitive to the delayed neurotoxic effects of TOCP. When studying OPIDN in rats, care must be exercised in choosing the experimental animal since some strains, e.g., F344, are not sensitive.
 ...
PMID:Lack of delayed neurotoxic effect after tri-o-cresyl phosphate treatment in male Fischer 344 rats: biochemical, neurobehavioral, and neuropathological studies. 335 6

Atropine, a postsynaptic muscarinic antagonist, and clonidine, a presynaptic inhibitor of acetylcholine release, protect mice from the lethal effects of soman, a potent and irreversible cholinesterase inhibitor. The purpose of this study was to determine the effects of atropine (6 mg/kg) and clonidine (0.2 mg/kg) on soman-induced lethality and behavioral changes in the rat. Soman produced a dose-dependent increase in lethality over a narrow concentration range (50-200 micrograms/kg, SC). Soman produced time- and dose-dependent increases in tremor, salivation, hind limb extension, convulsions and chewing behaviors, as well as decreases in three normal stereotyped behaviors, sniffing, locomotion and rearing. Atropine and clonidine were equally effective at limiting soman-induced lethality and behavioral changes. The protective effects of clonidine and atropine were synergistic, even though clonidine antagonizes some of the stereotyped behaviors elicited by atropine. Simultaneous pretreatment with clonidine and atropine completely eliminated the lethality and behavioral changes produced by injection of 200 micrograms/kg soman.
 ...
PMID:Behavioral effects of toxic doses of soman, an organophosphate cholinesterase inhibitor, in the rat: protection afforded by clonidine. 336 26

Mice pretreated with the centrally active alpha-2 adrenergic agonist, clonidine, were protected from several of the toxic manifestations of soman, an organophosphate acetylcholinesterase inhibitor. The protection resulted in increased survival rates and a reduction in centrally mediated symptoms of soman, including tremor and straub tail, as well as one peripheral muscarinic symptom, excessive salivation. Doses of clonidine between 0.1 and 1 mg/kg, administered between 5 and 40 min before LD80 to LD90 doses of soman, produced significant protection. Pretreatment with atropine (25 mg/kg) also protected against soman toxicity. When atropine was combined with clonidine, the degree of protection afforded by the combination was greater than that predicted for a simple additive effect. Mice protected by atropine from the initial toxicity of soman frequently died within 24 h; no such delayed lethality was observed with protective doses of clonidine. Clonidine noncompetitively inhibited acetylcholinesterase activity in vitro and after in vivo administration at protective doses. At brain concentrations obtained after in vivo administration in protective doses, clonidine also inhibited ligand binding to cortical muscarinic receptors in vitro. The protective effects of clonidine are likely to involve multiple effects, including blockade of acetylcholine release and postsynaptic muscarinic receptors and transient inhibition of acetylcholinesterase.
 ...
PMID:Clonidine protection from the toxicity of soman, an organophosphate acetylcholinesterase inhibitor, in the mouse. 376 Nov 96

The influence of clonidine on the toxicity produced by two irreversible, organophosphate cholinesterase inhibitors, soman and echothiophate, was studied in mice. At lethal doses, soman produced whole body tremor but no muscle fasciculation; at lethal doses, echothiophate produced muscle fasciculations but no whole body tremor. Pretreatment with clonidine protected against several toxic manifestations of soman, but had little effect on echothiophate toxicity. In addition to its documented effects on acetylcholine metabolism, clonidine was found to be a weak inhibitor of acetylcholinesterase. At certain concentrations, clonidine protected the enzyme from permanent inactivation by soman. These findings indicate that the toxicity of soman and echothiophate reflect primarily central and peripheral actions, respectively, and that clonidine has a much greater protective effect versus the centrally-acting agent. Moreover, direct interactions with acetylcholinesterase may contribute to clonidine protection from cholinesterase inhibitor toxicity.
 ...
PMID:Clonidine protection from soman and echothiophate toxicity in mice. 378 71

The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD50 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.
 ...
PMID:Genetically determined differences in acute responses to diisopropylfluorophosphate. 399 71

Using experimental models of parkinsonism, imitating the hypertonus of the parasympathetic system (hypokinesia, rigidity and tremor) following the intraperitoneal injection of the acetylcholinesterase inhibitor galanthamin (15 mg/kg) to mice, the authors showed that the m-cholinoblocker metamisyl (2 mg/kg) blocks all manifestations of the CNS parasympathetic hypertonus whereas the n-cholinoblocker eterofen (30 mg/kg) increases them. Based on the theory developed by the authors as to the reciprocity of interaction between the m- and n-cholinergic mechanisms within the framework of the single cholinergic system of the body, they offered the treatment of parkinsonism by the combined use of metamisyl (1-2 mg) and galanthamin (5-10 mg). Forty-five patients were treated with metamisyl alone and 40 patients with metamisyl coupled with galanthamin. The latter method of treatment proved to be more effective. The patients responded to the treatment immediately. It lasted 2-4 weeks. The follow-up showed that in some patients, the effect of the treatment stabilized and persisted for 4 weeks to 12 months without the use of the antiparkinsonian drugs. The authors emphasize that in cases of parkinsonism it is necessary to study and take into account the nature of changes in both intersystemic mediator interaction (between ACh and NA, ACh and D, ACh and 5-HT, etc.) and the intrasystemic one (between m- and n-cholino, alpha- and beta-adreno, D1 and D2, 5-HT1 and 5-HT2-ergic mechanisms).
 ...
PMID:[Method of treating parkinsonism with metamizil in combination with galanthamine (clinico-experimental basis)]. 399 98

Previous studies have shown indirectly that the neuromuscular effects of nonselective cholinesterase inhibitors are mediated through the inhibition of acetylcholinesterase (AChE). To test this hypothesis more directly we studied the effects of the specific inhibitor of AChE, BW 284c51, at the neuromuscular junction of rat diaphragms. BW 284c51 inhibits AChE in a dose-dependent partially reversible manner at all concentrations tested (10(-9) to 10(-4) M). Maximum inhibition was never greater than 92%. The drug increased miniature end-plate potential (MEPP) amplitude and prolonged half-decay time at 10(-7) and 10(-6) M. However, BE 284c51 had no effect on the resting membrane potential at any concentration. BW 284c51 at 10(-7) M reversibly increased MEPP frequency by almost 4-fold. There was a 2-fold increase in the occurrence of giant MEPPs in the presence of BW 284c51. The quantum content (m) of the end-plate potential was increased in 10(-7) M BW 284c51 as were end-plate potential amplitude and quantum size (q). Animals injected subcutaneously with 10 mg/kg of BW 284c51 displayed typical signs of AChE inhibition including salivation, whole body tremor and prostration. Spontaneous muscle fasciculation was more noticeable after in vivo injection of BW 284c51 than after in vitro administration. Furthermore, MEPP frequencies were considerably faster when the drug was injected in vivo than when applied in vitro. The data are discussed with respect to the hypothesis that inhibition of AChE causes presynaptic as well as postsynaptic effects.
 ...
PMID:Presynaptic and postsynaptic neuromuscular effects of a specific inhibitor of acetylcholinesterase. 625 19

Clonidine, an alpha-2 adrenergic agonist can inhibit the release of acetylcholine from central and peripheral cholinergic neurons. This study was designed to examine the ability of clonidine to protect animals from the toxic manifestations of cholinesterase poisoning. Physostigmine, a central and peripheral cholinesterase inhibitor produced tremors, and at high doses death, by respiratory paralysis. Mice were injected with physostigmine at a dose (0.75 mg/kg) which evoked tremors in 100% and death in 90% of the animals. Clonidine pretreatment (0.3 mg/kg) increased the onset latency to tremor from 5 to 20 min, increased the onset latency to death from 12 to 24 min and increased the percentage of survivors to 50%. Yohimbine (1 mg/kg) reversed these protective effects of clonidine. The physostigmine-induced accumulation of forebrain and hindbrain acetylcholine also was reduced by 50% in both brain regions in clonidine-pretreated mice. Neostigmine, a selective peripheral cholinesterase inhibitor, induced respiratory paralysis which was not affected by clonidine pretreatment. These findings indicate that central cholinergic neurons involved in the regulation of respiration and fine motor control, but not peripheral motor neurons, are inhibited by clonidine acting on alpha receptors.
 ...
PMID:Mechanism of the clonidine-induced protection against acetylcholinesterase inhibitor toxicity. 628 26


<< Previous 1 2 3 4 5 6 7 8 9 Next >>