1,720,971 research outputs found
Biochemical and electrophysiological studies on the mechanism of action of typical and atypical antidepressants on the H2-histamine receptor complex.
No full textCorrelation between histamine-induced neuronal excitability and activation of adenylate cyclase in the guinea pig hippocampus.
No full textIn a homogenate of guinea pig hippocampus histamine activated adenylate cyclase and in a hippocampal slice preparation it increased the firing rate of pyramidal cells in the CA3 region. Both activities were apparently mediated by H2 receptors. The concentration of histamine and of the H2 receptor agonist, impromidine, required to stimulate activity was similar in each test preparation with impromidine being about 100-fold more potent than histamine. Moreover, the H2 receptor antagonists, cimetidine and ICIA 5165, each reversed the activation by histamine of the two test preparations, with ICIA 5165 being about 100-fold more potent than cimetidine. Thus, there is a correlation between activation of cyclase and neuronal excitability induced by histamine. These observations support a large body of evidence suggesting that histamine is a neurotransmitter or modulator in the CNS
Muscarinic receptors modulate dopamine-activated adenylate cyclase of rat striatum
No full textWe investigated the effect of acetylcholine (ACh) on the activation of adenylate cyclase by dopamine (DA) in a lysed synaptosomal preparation from rat striatum. ACh reduced both basal and the DA-activated adenylate cyclase with an apparent IC50 of approximately 1 microM. From a kinetic analysis it appeared that ACh reduced the Vmax for activation by DA but not the activation constant for DA. For most preparations the Vmax was reduced by 30-40%. The presence of atropine did not affect the activation of the enzyme by DA but it blocked the inhibition by ACh. Following 6-hydroxydopamine lesion of the nigrostriatal pathway, the enzyme became supersensitive to activation by DA and also more sensitive to inhibition by ACh. Inhibition of adenylate cyclase by ACh appeared to be rather specific for activation by DA, as ACh had no effect on activation of adenylate cyclase by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. These results indicate that some striatal muscarinic and dopaminergic receptors are probably coupled to the same adenylate cyclase domain. Moreover, they suggest a biochemical model for the dynamic balance of cholinergic and dopaminergic neurons that innervate the striatum
Adenylate cyclase activity of synaptic membranes from rat striatum. Inhibition by muscarinic receptor agonists.
No full textAcetylcholine inhibits, by 30-40%, the basal adenylate cyclase activity of purified synaptic plasma membranes prepared from rat striatum (EC50 = 3 microM). Cholinergic receptor agonists inhibit this cyclase activity with the following rank order of potency: oxtremorine greater than acetylcholine greater than arecoline greater than methacholine greater than or equal to muscarine greater than or equal to carbachol greater than bethanechol. Nicotine fails to inhibit the cyclase, and d-tubocurarine fails to inhibit the action of cholinergic drugs. In contrast, atropine and scopolamine antagonize the effect of acetylcholine. The enzyme inhibition elicited by acetylcholine requires the presence of GTP, and disappears after intrastriatal injection of kainic acid. From these results, we infer that striatal adenylate cyclase can be modulated by muscarinic receptors
Inhibition of striatal adenylate cyclase activity by stimulation of muscarinic receptors
No full textThe dopamine receptor adenylate cyclase complex: evidence for post recognition site involvement for the development of supersensitivity.
No full textThe dopamine receptor adenylate cyclase complex of a rat striatal membrane preparation became more responsive to dopamine following the injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle or following the subcutaneous implantation of morphine pellets. Moreover, the membrane cyclase system was more responsive to activation by GTP, guanyl-5'-yl-imidodiphosphate and Mn-ATP. These observations suggest that both 6-OHDA and morphine induce similar biochemical changes in striatum and that the increased responsiveness arises, in part, from modification of the nucleotide regulatory and/or catalytic components of adenylate cyclase
Dynorphin and Prodynorphin mRNA Changes in the Striatum during Nicotine Withdrawal
No full textAbstract: Nicotine withdrawal causes somatic and negative affective symptoms that contribute to relapse and continued tobacco smoking. So far, the neuronal substrates involved are not fully understood, and an opioid role has been suggested. In this regard, the opioid dynorphin (Dyn) is of interest as it produces aversive states and has been speculated to play a role in the nicotine behavioral syndrome. These studies explore whether Dyn metabolism is altered during withdrawal following chronic administration of nicotine. Mice were administered nicotine, 2 mg/kg, s.c., four times daily for 14 days, and Dyn and prodynorphin (PD) mRNA estimated in selective brain regions at various times (30 min to 96 h) following drug discontinuation. The content of Dyn, estimated by RIA, was decreased in the striatum for a protracted time, from 30 min to over 72 h. In contrast, the mRNA for PD, evaluated by Northern blot, was elevated, appearing by 8 h and lasting over 96 h. Dyn was decreased in both ventral and dorsal striatum, and PD mRNA was differentially increased in the two striatal compartments as demonstrated by in situ hybridization. PD message was predominantly augmented in the nucleus accumbens, rostral pole, core, and shell, and the medial aspects of caudate/putamen. We interpret these data to indicate increased activity of striatal, particularly accumbal, dynorphinergic neurons during nicotine withdrawal resulting in enhanced peptide release and compensatory synthesis. Heightened dynorphinergic tone might be responsible, in part, for the emergence of the negative affective states observed during nicotine withdrawal
The muscarinic receptor adenylate cyclase complex of rat striatum: desensitization following chronic inhibition of acetylcholinesterase activity
No full textChronic inhibition of acetylcholinesterase activity by treatment with diisopropylfluorophosphate (DFP) decreased the capacity of acetylcholine (ACh) acting at a muscarinic receptor to inhibit basal adenylate cyclase activity in homogenates from rat striatum. There was also a loss of the capacity of ACh to inhibit the activation of adenylate cyclase by dopamine. The desensitization of the muscarinic receptor adenylate cyclase complex was associated with a marked attenuation of the capacity of ACh to stimulate a high-affinity GTPase activity present in striatal membranes. The EC50 value of ACh for inhibiting adenylate cyclas
Met-enkephalin and preproenkephalin mRNA changes in the striatum of the nicotine abstinence mouse
No full textA simple fluorometric method for cAMP: application to studies of brain adenylate cyclase activity.
No full textA simple fluorometric method for the determination of cAMP is presented. The fluorescent derivative is 1,N6-etheno cyclic 3,5-monophosphate (etheno-cAMP). Maximal formation of this derivative occurs after reacting cAMP with chloroacetaldehyde for 15 minutes at 100 degrees C. Fluorescent derivatives are also produced from compounds which contain a 6-amino purine. The specificity of the method resides in the use of a reverse phase/HPLC system. The derivatization as well as the fluorescent response of etheno-cAMP is linear between 2.5 and 700 picomoles of cAMP. Studies of brain adenylate cyclase by the fluorometric/HPLC method indicated that this method is comparable to the established radioenzymatic method. Thus, the present method provides a simple rapid nonradioactive means for the determination of adenylate cyclase activity
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