Synaptosomes rat brain

Figure 4. Binding was measured in rat brain synaptosomes using a rapid centrifugation technique. Total ( ), and nonspecific ( ) binding of tritiated PbTx-3 were measured, their difference representing specific binding (A). Rosenthal analysis yields a of 2.6 nM and a B of 6.0 pmol toxin bound/mg protein.

Figure 5. Comparison of specific displacement of 10 nM tritiated saxitoxin (A) or 10 nM tritiated PbTx-3 ( ) by unlabeled competitor saxitoxin or brevetoxin, respectively, in rat brain synaptosomes. IC q in each case is 5-10 nM.

Several brevetoxins have been examined for their respective abilities to competitively displace tritiated brevetoxin PbTx-3 from its specific site of action in brain synaptosomes. Analysis of IC q values revealed no marked differences in the displacing abilities between any of the type-1 toxins, and similarly there was no apparent difference between displacing abilities of PbTx-1 or -7, both type-2 toxins. Although some specific details require correlation, a gross comparison indicates that sodium channels in brain are similar in the systems examined. In the system studied most extensively, the rat brain synaptosome, t-test analysis revealed no significant differences between PbTx-2 and PbTx-3 IC q, or between PbTx-1 and PbTx-7 IC q, but statistically significant differences were found between the two classes (P<0.01) (5). If the Cheng-Prusoff equation (15) is applied ... 

Figure 6. Effect of brevetoxins on tritiated PbTx-3 binding to rat brain synaptosomes. Incubations, in the presence of 50 fig synaptosomal protein and 16 nM tritiated PbTx-3 with increasing amounts of unlabeled PbTx-1 ( ), PbTx-2 ( ), PbTx-3 ( ), PbTx-5 (A), PbTx-6 ( ), or PbTx-7 (o) were for 1 hr at 4 C. Each point represents the mean of three triplicate determinations.

Richelson, E and Pfenning, M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes most antidepressants selectively block noradrenaline uptake. Eur. J. Pharmacol. 104 277-286. 

A variety of side-chain modified analogs of MDMA and MBDB have begun to be examined. Very early studies were of the a,a-dimethyl analog, 3,4-methylenedioxyphentermine (figure 8a) and its N-methyl derivative (figure 10). This latter compound proved to lack MDMA-like activity (Shulgin, unpublished). Interestingly, this compound also lacked the ability to stimulate the release of [ H] serotonin from prelabeled rat brain synaptosomes (Nichols et al. 1982). 

G.K.W. Effects of certain hallucinogenie amphetamine analogs on the release of [ H]serotonin from rat brain synaptosomes. J Med Chem 25 530-535, 1982. 

FIGURE 2. Eadee-Scatchard transformation of saturation data of [ H]MDA binding in rat brain synaptosomes... 

Role of Lipophilicity in the Incorporation of [ H]MDA Into Rat Brain Synaptosomes... 

Zaczek, R., Culp, S., DeSouza, E.B. Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport. J. Pharmacol. Exp. Ther. 257 830, 1991. 

Yudkoff, M., Nelson, D., Daikhin, Y. etal. Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspar-tate shuttle. /. Biol. Chem. 269 27414-27420,1994. 

Brooks, M.W. and J.M. Clark. 1987. Enhancement of norepinephrine release from rat brain synaptosomes by alpha cyano pyrethroids. Pestic. Biochem. Physiol. 28 127-139. 

Ramadan, A.A., N.M. Bakry, A.S.M. Marei, A.T. Eldefrawi, and M.E. Eldefrawi. 1988. Action of pyrethroids on K+-stimulated calcium uptake by, and (3H)nimodipine binding to, rat brain synaptosomes. Pestic. Biochem. Physiol. 32 114-122. 

In an extension to the studies mentioned above, the actions of 11 commercial pyrethroids on calcium influx and glutamate release were assessed using a high-throughput approach with rat brain synaptosomes [75, 76]. Concentration-dependent response curves for each commercial pyrethroid were determined and the data used in a cluster analysis. Previously characterized Type II pyrethroids that induce the CS-syndrome symptoms (cypermethrin, deltamethrin, and esfenvalerate) increased calcium influx and glutamate release, and clustered with two other ot-cyano pyrethroids (p-cyfluthrin and A-cyhalothrin) that shared these same actions. Previously characterized Type I pyrethroids (bioallethrin, cismethrin, and fenpropathrin) did not share these actions and clustered with two other non-cyano pyrethroids (tefluthrin and bifenthrin) that likewise did not elicit these actions. 

Doherty JD, Nishimura K, Kurihara N, Fujita T (1987) Promotion of norepinephrine release and inhibition of calcium uptake by pyrethroids in rat brain synaptosomes. Pestic Biochem Physiol 29 187-196... 

Symington SB, Frisbie RK, Clark JM (2008) Characterization of 11 commercial pyrethroids on the functional attributes of rat brain synaptosomes. Pestic Biochem Physiol 92 61-69... 

Mercuric chloride is thought to gain access to the intracellular compartment through Na + and Ca2 + channels in the membrane [ 100]. Sulphydryl reagents, including Hg2 +, could inhibit K +-stimulated uptake of Ca2+ into rat brain synaptosomes in vitro [101]. In muscle sarcoplasmic reticulum, Hg2+ causes inhibition of ATP-dependent Ca2 + uptake and loss of accumulated calcium [ 102,103]. However, HgCl2 has been found to inhibit ATP-dependent calcium uptake more strongly than it inhibits potassium-stimulated uptake [ 104],... 

Poli MA, Mende TJ, Baden DG (1989) Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes. Mol Pharmacol 30 129-135 Pullaiah KC, Surapaneni RK, Rao CB, Albizati KF, Sullivan BW, Faulkner DJ, He CH, Clardy J (1985) Dictyoxetane, a novel diterpene from the brown alga Dictyota dichotoma from the Indian Ocean. J Org Chem 50 3665-3666... 

Mehorta and coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered 0.5-10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of calmodulin, indicating disruption of membrane Ca+2 transport mechanisms exogenous addition of calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater inhibition in brain preparations (Mehorta et al. 1989). However, endrin showed no inhibitory effects on the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes (Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the activities of adenylate cyclase or 3, 5 -cyclic phosphodiesterase, two enzymes associated with synaptic cyclic AMP metabolism (Kodavanti et al. 1988). 

Kodavanti PRS, Mehrota BD, Chetty SC, et al. 1988. Effect of selected insecticides on rat brain synaptosomal adenylate cyclase and phospodiesterase. J Toxicol Environ Health 25 207-215. 

Chetty SC, Aldous CN, Rashatwar SS, et al. 1983b. Effect of chlordecone on pH- and temperature-dependent substrate activation kinetics of rat brain synaptosomal ATPases. Biochem Pharmacol 32(21 ) 3205-3211. 

Desaiah D. 1985. Chlordecone interaction with catecholamine binding and uptake in rat brain synaptosomes. Neurotoxicology 6(1) 159-165. 

Desaiah D, Chetty CS, Prasada Rao KS. 1985. Chlordecone inhibition of calmodulin activated calcium ATPase in rat brain synaptosomes. J Toxicol Environ Health 16 189-195. 

Desaiah D, Trottman CH, Bansal SK. 1980b. Sensitivity of rat brain synaptosomal ATPases to several structurally related organochlorine compounds. Dev Toxicol Environ Sci 8 87-90. 

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