Browsing by Author "Ravina, Enrique"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- 5-HT2 antagonist activity of 3-aminomethyltetralonesPublication . Verde, Ignacio; Loza, M.; Castro, Maria Elena; Orallo, Francisco; Fontenla, José Angel; Calleja, José Maria; Ravina, Enrique; Cortizo, L.; Deceballos, M. L.The affinity of four 3-aminomethyltetralones for 5-HT2 receptors is reported, together with their inhibitory activity against serotonin-induced contractions in rat aorta rings stripped of endothelium. Compound 4, which has a p-fluorobenzoyl-piperidine fragment, exhibited activity similar to that of methysergyde.
- Antiserotoninergic activity of 2-aminoethylbenzocyclanones in rat aorta: Structure-activity RelationshipsPublication . Verde, Ignacio; Loza, Isabel; Ferreiro, T. G.; Sanz, F.; Lozoya, E.; Rodriguez, J.; Manaut, F.; Castro, Elena; Fontenla, José Angel; Cadavid, Isabel; Honrubia, M.; Fueyo, J.; Ravina, EnriqueSubcellular targeting of the components of the cAMPdependent pathway is thought to be essential for intracellular signaling. Here we have identified a novel protein, named myomegalin, that interacts with the cyclic nucleotide phosphodiesterase PDE4D, thereby targeting it to particulate structures. Myomegalin is a large 2,324-amino acid protein mostly composed of a-helical and coiled-coil structures, with domains shared with microtubule-associated proteins, and a leucine zipper identical to that found in the Drosophila centrosomin. Transcripts of 7.5–8 kilobases were present in most tissues, whereas a short mRNA of 2.4 kilobases was detected only in rat testis. A third splicing variant was expressed predominantly in rat heart. Antibodies against the deduced sequence recognized particulate myomegalin proteins of 62 kDa in testis and 230–250 kDa in heart and skeletal muscle. Immunocytochemistry and transfection studies demonstrate colocalization of PDE4D and myomegalin in the Golgi/centrosomal area of cultured cells, and in sarcomeric structures of skeletal muscle. Myomegalin expressed in COS-7 cells coimmunoprecipitated with PDE4D3 and sequestered it to particulate structures. These findings indicate that myomegalin is a novel protein that functions as an anchor to localize components of the cAMP-dependent pathway to the Golgi/centrosomal region of the cell.
- Pyridazine derivatives. XI: Antihypertensive activity of 3-hydrazinocycloheptyl[1,2-C]pyridazine and its hydrazone derivativesPublication . Gil-Longo, José; Laguna, Maria de los Reyes; Verde, Ignacio; Castro, Elena; Orallo, Francisco; Fontenla, Jose A.; Calleja, José Maria; Ravina, Enrique; Terán, Carmen3-Hydrazinocycloheptyl[1,2-c]pyridazine (4) and its hydrazone derivatives 3-[N1-(isopropylidene)]hydrazinocycloheptyl[1,2-c]pyridazine [correction of hydrazinocyclohexyl] (5) and 3-[N1-(isobutylidene)]hydrazinocycloheptyl[1,2-c]pyridazine (6) were prepared, and their activity against genetic, neurogenically-induced, and deoxycorticosterone acetate -NaCl-induced hypertension was found to be at least as great as that of hydralazine. The results of studying vasorelaxation of rat aorta by 4 and hydralazine suggest that both these compounds owe their antihypertensive activity to direct relaxation of vascular smooth muscle.