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Effect of serotonin (5-HT) on trigeminal rhythmic activities generated in in vitro brainstem block preparations.

We used rat isolated brainstem block preparations to analyze the functional roles of serotonin receptors in the generation of trigeminal rhythmic activities. We previously reported that trigeminal rhythmic activities could be induced by some pharmacological applications in an isolated brainstem preparation with a rostral boundary at the border between the inferior and superior colliculus, and a caudal border at the level of the rostral facial nucleus. However, the same stimulation did not induce trigeminal rhythmic activities in a whole brainstem block preparation with the same rostral boundary and a caudal border at the obex level. In the present study, both the 5-HT(1A) phthalimido-butyl-piperazine, and the 5-HT(2C) agonist, 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane, combined with N-methyl-D,L-aspartate and bicuculline, elicited trigeminal rhythmic activities in a whole brainstem block preparation. Our results suggest that serotonin has both facilitation and inhibition effects on the generation of trigeminal rhythmic activities in an isolated brainstem block preparation in vitro.

Animals↗

Origin of the ATP formed during the light-dependent oxygen uptake catalyzed by Rhodospirillum rubrum chromatophores.

The oxygen uptake which is observed when Rhodospirillum rubrum chromatophores are illuminated under air and in the presence of reduced 2, 6-dichlorophenolindophenol (DCIP), 2, 3, 5, 6-tetra-methyl-P-phenylenediamine (diaminodurene, DAD) or N, N'-tetramethyl-p-phenylenediamine (TMDP) depends on the electron-donor concentration according to the equation of Michaelis-Menten. The apparent Km for the donor is lowered by the electron-transfer inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) which causes therefore a stimulation of the rate of the reaction at non-saturating concentrations of the donors. In contrast, the ATP formation which takes place simultaneously to oxygen uptake does not show an enzyme-like dependence on donor concentration. Moreover it is inhibited by HQNO to a variable extent, depending on the particular donor present and on its concentration. Therefore it appears that the HQNO-sensitive phosphorylation is coupled to a cyclic flow which coexists and competes with the non-cyclic flow from donor to oxygen. In the presence of HQNO, substrates and uncouplers of ATP formation accelerate somewhat the rate of the oxygen uptake supported by reduced DCIP and DAD. Thus part of the HQNO-resistant phosphorylation seems to be associated with the non-cyclic flow from those tow donors to oxygen. The lack of stimulation by phosphorylation or by uncoupling of the TMPD-supported oxygen uptake does not permit a conclusion as to whether this reaction is coupled to ATP formation or not. Another part of the HQNO-resistant ATP formation is independent of the presence of oxygen and appears to be associated to cyclic flows which bypass the HQNO site. This type of phosphorylation is most important in the presence of TMPD.

Adenosine Triphosphate↗

Hemoglobin E, an oxidatively unstable mutation.

When bloods from 3,159 individuals from the United States, Iran, Ethiopia, and South Vietnam were examined for erythrocytic enzyme deficiencies with a new test utilizing the visible reduction of 2,6-dichlorophenolindophenol by glutathione, gross turbidity was observed in 81 samples. All were from Southeast Asia and 78 contained hemoglobin E. The precipitation rates of various hemoglogins in hemolysates incubated with dichlorophenolindophenol were: Hb EE greater than Hb AE greater than other hemoglobins (A, S, C, D, A2, F, O-Arabia, Rush). Hemoglobin E is an oxidatively unstable hemoglobin, possibly with weakened alpha 1 beta 1 contact; it may result in increased susceptibility to oxidative hemolysis and can be simply detected and differentiated from both Hb C and Hb O-Arabia.

Blood Protein Electrophoresis↗

DOI, an agonist of 5-HT2A/2C serotonin receptor, alters the expression of cyclooxygenase-2 in the rat parietal cortex.

The hallucinogenic effect of DOI, serotonin 5-HT2A/2C receptor agonist, is known to be associated with the activation of cortical 5-HT2 receptors. However, the effect of DOI on excitability of cortical neurons and their subsequent function is still not quite understood. Previous immunohistochemical studies using Fos proteins expression as a marker of neuronal activity showed the involvement of arachidonic acid cascade, particularly cyclooxygenase metabolic pathway, in DOI-induced Fos proteins expression in the rat parietal cortex. DOI increases arachidonic acid release which is transformed itself via acceleration of cyclooxygenase metabolic pathway to biologically active metabolites, such as prostaglandins and thromboxanes. Since cyclooxygenase-2 (COX-2) expression correlates with neuronal activity, it was of interest to investigate whether DOI is capable of influencing the level of COX-2 protein and mRNA expression in the rat parietal cortex. It was observed that neurons which were positive for 5-HT2A receptors showed constitutive COX-2 immunoreactivity. It was found further, that COX-2 protein level was increased at 1 h, and returned to the control level at 3 and 6 h after DOI (5 mg/kg) administration. In contrast, DOI decreased the COX-2 mRNA expression at all tested time points (1 h, 3h and 6h after DOI treatment). The obtained results further support the suggestion that COX-2 activation and possibly arachidonic acid metabolites generated by COX-2 may be considered as important mediators of functional responses generated by activation of cortical 5-HT2A/2C receptors.

Animals↗

Reversible disorganization of the locomotor pattern after neonatal spinal cord transection in the rat.

The central pattern generators (CPGs) for locomotion, located in the lumbar spinal cord, are functional at birth in the rat. Their maturation occurs during the last few days preceding birth, a period during which the first projections from the brainstem start to reach the lumbar enlargement of the spinal cord. The goal of the present study was to investigate the effect of suppressing inputs from supraspinal structures on the CPGs, shortly after their formation. The spinal cord was transected at the thoracic level at birth [postnatal day 0 (P0)]. We examined during the first postnatal week the capacity of the CPGs to produce rhythmic motor activity in two complementary experimental conditions. Left and right ankle extensor muscles were recorded in vivo during airstepping, and lumbar ventral roots were recorded in vitro during pharmacologically evoked fictive locomotion. Mechanical stimulation of the tail elicited long-lasting sequences of airstepping in the spinal neonates and only a few steps in sham-operated rats. In vitro experiments made simultaneously on spinal and sham animals confirmed the increased excitability of the CPGs after spinalization. A left-right alternating locomotor pattern was observed at P1-P3. Both types of experiments showed that the pattern was disorganized at P6-P7, and that the left-right alternation was lost. Alternation was restored after the activation of serotonergic 5-HT(2) receptors in vivo. These results suggest that descending pathways, in particular serotonergic projections, control the strength of reciprocal inhibition and therefore shape the locomotor pattern in the neonatal rat.

Animals↗