Adenylic 1-methyl

Forskolin (5-[acetyloxy]-3-ethenyldodecahydro-6,10,10b-trihydroxy-3,4a,7,7,10a-penta-methyl-[3R- 3a-4aP, SP, 6P, 6aa,10a, lOaP, 10ba -lFf-naphtho[2,l-b]pyran-l-one) [66575-29-9] M 410.5, m 229-232°, 228-233°. Recrystd from CfiH6-pet ether. It is antihypertensive, positive ionotropic, platelet aggregation inhibitory and adenylate cyclase activating properties [Chem AbstrS9 1978 244150, de Souza et al. Med Res Rev 3 201 1983]. 

Imidazolides of adenylic acid (ImpA) or uridylic acid (ImpU) are polycondensed to oligonucleotides by means of Zn2+ ions. 1673 The resulting phosphordiester bond was found to be of the 2, 5 type. In the reaction of nucleoside 5 -phosphoric acid methyl ester with ImpA in the presence of MgC, 2, 5 -dinucleotides are formed six to nine times more frequently than the corresponding 3, 5 compounds. 63 Polycondensations of ImpA in aqueous solution in the presence of various divalent metal ions lead to short oligo-adenylic acids (pA) (n = 1—5) mainly with 2, 5 -intemucleotide linkages. With Pb2+, for example, the total yield of oligomers was as high as 57%. 1683 1693... 

Enzymes catalysing the transfer of a chemical group, (transfer methyl, acyl, etc.) (EC 2.1 - 2.9) EC2.1 Transf. one-carbon groups (nicotinamide N- Adenylate/creatine kinase/firefly AMP, ADP, ATP ATP Luciferin / Mg21- 19... 

Lapin EP, Weissbarth S, Maker HS, et al. 1982. The sensitivities of creatine and adenylate kinases to the neurotoxins acrylamide and methyl n-butyl ketone. Environ Res 28 21-31. 

Theoretical explanations for the stimulatory activity of the methyl xanthines. These compounds inhibit phosphodiesterase reaulting in the prolonged activ of metabolic enzymes.Adenylate cyclase activity is modulated by the bindin free adenosine. The methyl xanthines are antagonists to adenosine but the bindings do not produce its modulating (inhibitory, attenuating) response. Therefore the end result is stimulatory in relation to cAMP activity. 

Apart from forskolin, a number of other manoyl oxides have been shown to interact with the AC enzyme system. Biotransformation of certain ent- 3-epi-manoy oxides by Curvularia lunata resulted in compounds functionalized in C-3 or in C-3 and C-12, which exhibited an AC stimulatory effect, although milder than that of forskolin (about 30 times less) [173]. The same activity was also ascribed to some synthetic derivatives of en/-8a-hydroxy-13 (16), 14 dien-18-oic acid methyl ester [178,179], The biotransformation of ent-manoyl oxide-16-hydroxy 18-oic acid methyl ester with Rhizopus nigricans, however, resulted in carbomanoyl oxide which showed a selective inhibitory action on the activity of adenylate cyclase depending on the material initially used to stimulate the enzyme. This manoyl oxide inhibited the activity of the enzyme previously stimulated by forskolin but not by glucagon. A manoyl oxide ent-3fi, 6/ -dihydroxy-13-e/ z-manoyl oxide) which also inhibited the activity of AC, was produced from the biotransformation of... 

It has been reported that RNase T2 is able to split easily the phosphodiester bond of 1-methyl adenylic acid in methylated RNA 32) and 1-methyl adenylyl-(3 -5 ) -uridine 30). However, the Ap-N-oxide phosphodiester bonds in RNA-N-oxide, prepared by the action of perphthalate on RNA, were found to be quite resistant to RNase T2 85). The phos-... 

Signal transduction was studied most precisely for the 5-HTiA receptor in rat amygdala (Koyama et al. 1999). The receptor operated through a N-methyl maleimide-sensitive mechanism and by adenyl cyclase inhibition rather than any change in K+ or Ca2+ channels. The fall in cyclic AMP presumably was followed by decrease in the phosphorylation of synaptic vesicle proteins and, finally, in a decrease of exocytosis. 

The dipeptide L,L-0-(methyl-serinyl)valine was formed without significant loss of label, and at the same time, no label was observed in the AMP released. This result thus excludes a thioester intermediate, which by thiolysis of the adenylate would have led to an even distribution of the 180 between AMP and Val. However, the isomeric dipeptide L,D-0-(methyl-serinyl)valine was recovered with all possible labeling patterns of 180180, 160180, and 160160 [69], To explain the retainment of label in the epimerized dipeptide is not easy. Baldwin and colleagues propose an alternative direct acyl transfer mechanism operating with dipeptidyl adenylates of the type Cys-Val, being epimerized, and transferred to... 

In either the presence or absence of GTP, half-maximal stimulation of enzyme activity is achieved with 3 uM dopamine. Both 6,7-ADTM and epinine (K-methyl dopamine) stimulate adenylate cyclase activity to the same degree as does dopamine (Figure 8). In contrast, apomorphine is a partial agonist eliciting only 30 of the maximal effect of dopamine. The dopamine-stimulated adenylate cyclase activity is selectively blocked by cis-flupenthixol rather than the trans-isomer of this antagonist (JJL). Among the antagonists tested, the order of potency is cis-flupenthixol = fluphenazine > chlorpromazine > haloperidol > trans-flupenthixol (Table I). 

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