1,721,114 research outputs found
Beta-adrenergic receptor regulation of a cyclic nucleotide phosphodiesterase in C6 glioma cells
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Regulation of intracellular and nuclear metabolism by stimulation of beta-adrenergic receptors on C6 glioma cells
No full textPertussis toxin attenuates D2 inhibition and enhances D1 stimulation of adenylate cyclase by dopamine in rat striatum
No full textThe response of adenylate cyclase to GTP and to dopamine (DA) was investigated in synaptic plasma membranes isolated from rat striatum injected with pertussis toxin, which inactivates the inhibitory guanine nucleotide-binding regulatory protein (Ni) of adenylate cyclase. Pertussis toxin treatment reverted the inhibitory effects on the enzyme activity elicited by micromolar concentrations of GTP and reduced by 50% the DA inhibition of cyclase activity via D2 receptors. The toxin treatment enhanced the net stimulation of enzyme activity by DA in the presence of micromolar concentrations of GTP. However, the stimulatory effect of the selective D1 receptor agonist SKF 38393 was not significantly affected. The data indicate that Ni mediates D2 inhibition of striatal adenylate cyclase and participates in the modulation of D1 stimulation of the enzyme activity by DA
Pharmacological and biochemical characterization of dopamine receptors mediating stimulation of a high affinity GTPase in rat striatum
No full textIn synaptic plasma membranes of rat striatum, activation of dopamine receptors stimulates a high affinity GTPase activity. The rank order of potency of various dopamine receptor agonists in increasing GTP hydrolysis is the following: (-)-propylnorapomorphine greater than (-)-apomorphine = (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene [(+/-)-A-6,7-DTN] greater than dopamine = LY 171555 greater than noradrenaline. The selective D-1 dopamine receptor agonist, SKF 38393, does not produce a significant increase in GTP hydrolysis. Moreover, the dopamine-stimulated GTPase activity is completely reversed by the D-2 receptor antagonists, 1-sulpiride and zetidoline, but not by the selective D-1 antagonist SCH 23390. Na+ modulates the dopamine receptor-regulated GTP hydrolysis by increasing the percentage of stimulation and decreasing the agonist potency. Intrastriatal injection of pertussis toxin, which impairs the function of the inhibitory guanine nucleotide binding regulatory protein (Ni) of adenylate cyclase, significantly reduces the dopamine stimulation of striatal GTPase activity and the dopamine inhibition of adenylate cyclase. In contrast, cholera toxin, which blocks the stimulation of GTPase activity by hormones which increase adenylate cyclase activity, does not modify the dopamine-stimulated GTPase activity. These data indicate that the stimulation of GTPase activity elicited by dopamine results from activation of the D-2 type of dopamine receptors and is expression of the increased turnover of GTP at the level of Ni. The results are consistent with the idea that Ni is involved in the inhibitory coupling of striatal D-2 receptors to adenylate cyclase
Positive coupling of cholinergic muscarinic receptors to adenylate cyclase activity in membranes of rat olfactory bulb
No full textIn membranes of rat olfactory bulb acetylcholine stimulated adenylate cyclase activity in a concentration-dependent manner. The maximal stimulation corresponded to 53% increase of basal enzyme activity and was obtained with 100 microM acetylcholine. The concentration of the cholinergic agonist eliciting a half-maximal effect was 0.4 microM. The stimulatory effect of acetylcholine was antagonized by 0.1 microM atropine but not by 10 microM (+)-tubocurarine. Moreover, the addition of micromolar concentrations of GTP was absolutely required for the enzyme stimulation by acetylcholine. The results demonstrate the presence in rat olfactory bulb of muscarinic receptors coupled to stimulation of adenylate cyclase probably via a GTP regulatory protein and provide evidence for a novel signal transduction mechanism of central muscarinic receptors
Muscarinic stimulation of adenylate cyclase activity of rat olfactory bulb. II. Characterization of the antagonist sensitivity and comparison with muscarinic inhibitions of the enzyme in striatum and heart.
No full textThe pharmacological profile of the muscarinic stimulation of adenylate cyclase activity in rat olfactory bulb was investigated by using a number of antagonists with different selectivity for the muscarinic receptor subtypes. Schild analysis showed that this response was counteracted with the following rank order of potency: R(-)quinuclidinyl benzilate greater than atropine greater than RS(+/-)-3-quinuclidinyl xanthene-9-carboxylate hemioxalate greater than S(+)quinuclidinyl benzylate greater than 4-diphenylacetoxy-N-methylpiperidine methbromide greater than secoverine greater than methoctramine greater than dicyclomine greater than hexahydrosiladifenidol greater than p-fluorohexahydro-sila-difenidol greater than AF-DX 116 greater than pirenzepine. In the heart and corpus striatum, the antagonist rank orders of potency in counteracting the muscarinic inhibition of adenylate cyclase activity were consistent with the involvement of homogeneous populations of M2 and M3 receptors, respectively. Conversely, in the olfactory bulb, the pirenzepine inhibition curve of acetylcholine-stimulated enzyme activity was biphasic, with a major component of the response being inhibited with low affinity. These results indicate that more than one receptor subtype may participate in the stimulation of adenylate cyclase in rat olfactory bulb. The predominant receptor involved appears to be different from the M1, M2 and M3 subtypes and pharmacologically equivalent to the m4 gene product
Sodium ions and GTP decrease the potency of [Nphe1]N/OFQ(1-13) NH2 in blocking nociceptin/orphanin FQ receptors coupled to cyclic AMP in N1E-115 neuroblastoma cells and rat olfactory bulb
No full textThe pseudopeptide [Nphe(1)]N/OFQ(1-13)NH(2) (Nphe) has been shown to act as a pure, selective and competitive antagonist of nociceptin/orphanin FQ (N/OFQ) receptors in different tissues. However, Nphe displayed a highly variable potency, with pA(2) values ranging from 5.96 to 8.45. In the present study, we show that sodium ions and GTP markedly affect the potency of Nphe in blocking N/OFQ receptors coupled to cyclic AMP inhibition in different cellular systems. In intact N1E-115 neuroblastoma cells, the pA(2) value of Nphe increased from 7.13 to 8.02 when the extracellular sodium concentration was reduced from 138 to 2.5 mM. When N/OFQ inhibition of adenylyl cyclase activity was assayed in cell membranes, 100 mM NaCl decreased the pK(i) value of Nphe from 8.38 to 7.32, but increased that of the nonpeptide N/OFQ receptor antagonist CompB from 8.61 to 8.92. Similar effects of sodium ions on the potencies of Nphe and CompB were observed when the compounds were used to antagonize the N/OFQ inhibition of adenylyl cyclase activity in membranes of the external plexiform layer of the rat olfactory bulb. In the same assay, the increase of GTP concentration from 0.1 to 200 micro M decreased Nphe potency by 8-fold. These data demonstrate that sodium ions and GTP affect the potency of Nphe in a manner similar to that of agonists but not of pure antagonists and suggest that these factors may contribute to the reported variability of Nphe affinity constant
Activation of adenosine A1 receptor by N6-(R)-phenylisopropyladenosine (R-PIA) inhibits forskolin-stimulated tyrosine hydroxylase activity in rat striatal synaptosomes.
No full textWe investigated the effect of the relatively selective A1 adenosine receptor agonist N6-(R)-phenylisopropyladenosine (R-PIA) on tyrosine hydroxylase activity (TH) of synaptosomes obtained from rat striatum. TH activity was assayed in supernatant obtained following sonication and centrifugation of the tissue preincubated with the test compounds. R-PIA produced a modest decrease of basal enzyme activity, but significantly reduced the activation of the enzyme by submaximal (0.1-0.5 microM) concentrations of forskolin (FSK) a stimulator of adenylate cyclase. The IC 50 value of R-PIA was 17 nM and the maximal inhibition corresponded to 30-40% decrease of the enzyme activity stimulated by FSK. The S-isomer of PIA failed to affect TH activity under control and stimulated conditions. Moreover, the inhibitory effect of R-PIA was completely antagonized by 8-cyclopentyl- 1,3 -dimethylxanthine, an adenosine receptor blocker. R-PIA inhibited both basal and FSK-stimulated adenylate cyclase activity. These results indicate that in striatal dopaminergic terminals TH activity can be modulated in an inhibitory manner by activation of presynaptic A1 adenosine receptors
PACAP is a potent and highly effective stimulator of adenylyl cyclase activity in the retinas of different mammalian species
No full textIn rat, calf, pig and rabbit retinas the two forms of pituitary adenylate cyclase activating polypeptide with 38- and 27-amino acids (PACAP-38 and PACAP-27) produce a robust stimulation of adenylyl cyclase activity. PACAP-38 acts at picomolar concentrations and is generally more potent than PACAP-27. Both PACAPs are systematically more effective than the structurally homologous vasoactive intestinal peptide. Moreover, rat, calf and pig retinas contain significant amounts of PACAP-38 immunoreactivity. This study provides the first evidence for the action and occurrence of PACAP in mammalian retinas
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