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J M Musacchio

Publications and source records attributed to J M Musacchio.

71 records · Page 4Linked to original sources
PubMed1975

Interactions of morphine, adenosine, adenosine triphosphate and phosphodiesterase inhibitors on the field-stimulated guinea-pig ileum.

Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index to the relative potency of various narcotic analgesics. This property suggests that this preparation might be used as a model in attempts to elucidate the mechanism(s) by which morphine induces analgesia in the central nervous system. Since it has been demonstrated that some adenosine derivative may function as an endogenous inhibitory transmitter in the gut, the effects of adenosine, adenosine triphosphate (ATP) and morphine on the ileum were further characterized and compared. Morphine, adenosine and ATP produce a substantial inhibition of the isometric contractions induced by transmural field stimulation. The inhibition produced by each is antagonized by 2.5 times 10(-7) M tolazoline whereas that produced by ATP is potentiated by 4 times 10(-7) M 5-hydroxytryptamine. The inhibitory effects of morphine and ATP can also be markedly potentiated by two of the several phosphodiesterase inhibitors tested, Ro 20-1724 and dipyridamole. In addition, pretreatment of the ileum with either adenosine, ATP or morphine can produce a significant potentiation of the inhibitory effects of norepinephrine. The above suggests that cyclic adenosine 3',5'-monophosphate may play a role in mediating some of the inhibitory effects produced by exogenous adenosine, ATP and morphine. In addition, the similarities between the effects produced by these substances indicates that the biochemical pathways responsible for mediating the effects of each may share some common elements.

Adenosine↗
PubMed1971

Dihydropteridine reductase: implication on the regulation of catecholamine biosynthesis.

The low tissue concentrations of tetrahydrobiopterin, as well as the antagonism between the catecholamine feedback inhibition of tyrosine hydroxylase and the reduced cofactor concentrations, suggest that dihydropteridine reductase may play an important role in the regulation of catecholamine biosynthesis. The interaction of the different components involved in the hydroxylation of tyrosine was studied in vitro in a complex system composed of tyrosine hydroxylase, dihydropteridine reductase, and the different cofactors. This system has several important characteristics: (a) the rate of dihydroxyphenylalanine formation can be controlled by the concentration of dihydropteridine reductase; (b) low concentrations of catecholamines (2 x 10(-5) M) can produce a marked inhibition of tyrosine hydroxylase activity; and (c) the catecholamine feedback-inhibition of tyrosine hydroxylase can be antagonized by increasing concentrations of dihydropteridine reductase. The properties of the in vitro tyrosine hydroxylase-dihydropteridine reductase system suggest that dihydropteridine reductase may have an important role in vivo in the determination of the rates of dihydroxyphenylalanine formation and on the effectiveness of the catecholamine feedback-inhibition of tyrosine hydroxylase activity.

Adrenal Glands↗
PubMed1969

Increase in rat brain tyrosine hydroxylase activity produced by electroconvulsive shock.

A sustained increase in the turnover of norepinephrine coupled with an increased concentration of that amine has, in a previous study, been observed in the brains of rats exposed to electroconvulsive shock twice daily for one week. The phenomenon has been further examined by studying the effects of a similar regimen of electroconvulsive shock upon tyrosine hydroxylase in the brain, since that enzyme appears to be rate-limiting in norepinephrine synthesis. A small (15%) but significant increase in the whole brain enzyme activity was found in the electroshock-treated animals. A significant increase of tyrosine hydroxylase activity was found in the brainstem (24%) and cortex (20%) of such animals.

Animals↗
PubMedDate not supplied

Processing of enkephalin precursors by chromaffin granule enzymes.

Subcellular localization studies indicate that the enzyme activities which cleave enkephalins from larger polypeptides are located in both membranous and soluble components of the chromaffin granules and not in the lysosomes. Cleavage of endogenous precursors produced methionine enkephalin [Met-E], leucine enkephalin [Leu-E], and Met-E-Arg6. Cleavage of synthetic peptide E produced Leu-E, Met-E, and Met-E-Arg6. The pH optimum for enkephalin production is pH 5.7. Dithiothreitol prevents the inhibition of enkephalin conversion produced by p-chloromecurobenzoate. Studies with peptide E indicate that cleavage appears to occur at pairs of basic amino acid residues. The presence of enkephalin producing enzymes with the precursors and the products in the chromaffin granules could be important in the elucidation of the factors that regulate enkephalin biosynthesis.

Animals↗