Serotonin 5-HT2C Receptor Stimulates Cyclic GMP Formation in Choroid Plexus

Abstract: The serotonin 5-HT_2C receptor (formerly designated the 5-HT_1C receptor) of the choroid plexus triggers phosphoinositide turnover. In the present study, we demonstrate that receptor activation also triggers the formation of cyclic GMP (cGMP). Application of 1 µM 5-HT to porcine choroid plexus tissue slices resulted in stimulation of cGMP formation to a maximum of five-fold basal level, with an EC₅₀ of 11 nM. This response was not inhibited by muscarinic or β-adrenergic receptor antagonists. Serotonin receptor antagonists inhibited cGMP formation with apparent K_i values of 1.3 (mianserin), 200 (ketanserin), and 5,500 (spiperone) nM, respectively. Neither serotonin-stimulated cGMP formation nor PI turnover was inhibited by pertussis toxin pretreatment. Preliminary biochemical studies suggested that serotonin-stimulated cGMP formation was calcium, phospholipase A₂, and lipoxygenase dependent, as incubation in low calcium buffers or inclusion of the phospholipase A₂ or lipoxygenase inhibitors p-bromophenacyl bromide or BW 755c resulted in significant reduction of cGMP formation. The present results suggest that in addition to triggering phosphoinositide turnover, choroid plexus serotonin 5-HT_2C receptors trigger cGMP formation in a calcium-sensitive manner.     

External longitudinal splitting of the tibialis anterior muscle for coverage of compound fractures of the middle third of the tibia

In this modern era, compound fractures of the middle third of the tibia are relatively common. With the advent of external fixation, these fractures can be more rapidly and effectively dealt with, and attention can be directed to immediate coverage of the exposed bone. External longitudinal splitting of the anterior tibialis muscle offers a convenient and safe method for converting the open fracture to a closed one. The uniqueness of the tibialis anterior muscle is two-fold. It is circumpennate, and it has an internal axial tendon corresponding to almost its total length. Both these features impart to it considerable strength, and the muscle splitting herewith described does not appear to impair its function. Five treated limbs, each with loss of soft tissues overlying compound mid-third tibial fractures, are presented. Rapid healing and virtual absence of bone infection was observed in all cases.     

The effect of tetrahydrobiopterin on the in situ phosphorylation of tyrosine hydroxylase in rat striatal synaptosomes

Tetrahydrobiopterin (BH₄), the obligatory cofactor of the aromatic amino acid hydroxylases, decreased the in situ³²P-phosphorylation of tyrosine hydroxylase (TH) in rat striatal synaptosomes. Incubation of pre-³²P-labeled synaptosomes with BH₄ in the presence of a permeant analogue of cAMP decreased the cAMP-stimulated level of³²P label incorporation into TH by about 50%, as determined by immunoprecipitation and autoradiography of SDS-polyacrylamide gels. The extent of inhibition mirrored changes in intrasynaptosomal BH₄ levels and varied both as a function of BH₄ concentration and length of incubation. A similar decrease in the amount of TH³²P-labeling was observed with the precursor of BH₄, sepiapterin. This effect, in turn, was reversed by the inhibitor of sepiapterin reductase, N-acetyl-serotonin. Finally, exposure of pre-³²P-labeled synaptosomes to the inhibitor of protein phosphatase 2A, okadaic acid, blocked the response to BH₄. Collectively, the data suggest that BH₄ stimulates the dephosphorylation of TH in situ and thus may play a dual role both as a cofactor for catalysis and a regulator of hydroxylase activity.Special issue dedicated to Dr. Bernard W. Agranoff.     

Oxygen consumption and ammonia excretion in the detritivore caddisfly Limnephillus sp. exposed to low pH & aluminum

Respiration and excretion were measured relative to pH and aluminum in three nymphal weight groups of a detritivore caddisfly. Although a reduction in respiration rates was consistently observed within all stages exposed to a pH of 4 and 0.3 mg 1⁻¹ of aluminum, the differencewas not statistically significant among treatments. Excretion rates, on the other hand, were significantly increased throughout the low pH treatment, but not when exposed to low pH and aluminum combined. The derived O:N ratios indicate low pH causes a shift to a protein-oriented metabolism which was most pronounced in the smallest size group. Aluminum mitigates this effect.     

Über die Degenerationserscheinungen während der intrauterinen Entwicklung bei Salamandra maculosa

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