Biomedical subjects
Publications and source records attributed to S Uma.
Some new thiazolo[3,2-a]pyrimidine derivatives were prepared refluxing 2-thioxo-1,2,3,4-tetrahydropyrimidine derivatives with phenacyl bromide in glacial acetic acid. Calcium antagonistic activities of these compounds were evaluated in K(+)-depolarized rat aorta, using nifedipine as reference compound.
A series of 1,2,3,4-tetrahydro-6-methyl-4-(substituted phenyl)-2-thioxo-5-pyrimidinecarboxylic acid methyl esters were synthesized by condensing thiourea with methyl acetoacetate and nonsubstituted or differently substituted benzaldehydes in absol. ethanol using HCl as a catalyst according to the Biginelli reaction. The structures of the compounds were confirmed by elemental and spectroscopic analysis. -The compounds were evaluated for their calcium antagonistic activity on the basis of their potency in inhibiting [3H] PN 200-110 binding on microsomes obtained from rat skeletal muscle.
The contractile effect of 5-HT in the isolated common bile ducts of guinea-pigs was studied. 5-HT, administered non-cumulatively, evoked contractions which were concentration-dependent. Responses due to the low concentrations of 5-HT were antagonised significantly by ketanserin (10(-7) M and 10(-6) M) and methysergide (10(-6)M and 10(-5) M) whereas those induced by the higher concentrations of 5-HT remained unchanged. Atropine (3 x 10(-8) and 10(-7) M) and ICS 205-930 (10(-7) M and 10(-6) in contrast inhibited the contractions elicited by high concentrations of 5-HT without altering significantly the responses due to the lower ones. The results led us to conclude that 5-HT evoked contractions at low concentrations are predominantly mediated by 5-HT2 receptors whereas those at high concentrations are dependent on acetylcholine release via the stimulation of 5-HT3 receptors.
In guinea-pig common bile duct serotonin (5-HT) (10(-7)-10(-5) M) administered cumulatively caused dose-dependent inhibition of the twitches evoked by electrical field stimulation (0.3 ms, 0.1 Hz, supramaximal voltage). Maximum inhibition was 86 +/- 2% of the control twitch amplitude. The effect was mainly due to a presynaptic mechanism since acetylcholine induced contractions were not influenced by 5-HT. This inhibitory action was unaffected by ketanserin (10(-6) M), ICS 205-930 (10(-6) M) and yohimbine (10(-6) M) indicating the lack of involvement of 5-HT2, 5-HT3 and alpha-2 adrenergic receptors respectively. Metoclopramide (3 x 10(-6)-3 x 10(-5) M) per se increased the twitch height and antagonized the 5-HT effect in a non-competitive manner. Methysergide (10(-7)-10(-5) M) also prevented the twitch inhibition and the mode of blockade was not consistent with simple competitive antagonism. The results suggest that presynaptically located 5-HT receptor differs in its pharmacological properties from other neuronal 5-HT receptors.
Several 1,2,3,4-tetrahydro-6-methyl-4-(substituted phenyl)-2-thioxo-5-pyrimidinecarboxylic acid methyl esters were synthesized by condensing thiourea with methyl acetoacetate and substituted benzaldehydes according to Biginelli reaction. The structures of the compounds were confirmed by spectral and elemental analysis and their calcium antagonistic activities were investigated. Furthermore, the compounds synthesized in previous and present studies were evaluated for their antiaggregating activities.
The effects of phenylephrine and noradrenaline have been investigated on the perfusion pressure of the rat isolated lung. Both drugs (0.3-30 micrograms) produced a dose-dependent decrease in perfusion pressure elevated by 20 mM KCl, which was reversed to a dose-dependent increase after addition of propranolol (1 x 10(-7) M) to the perfusion fluid. Increments due to both agonists in the presence of propranolol were antagonized by prazosin (1 x 10(-6) M). Propranolol, but not prazosin, elevated the basal perfusion pressure. The results indicate that phenylephrine and noradrenaline are more effective in stimulating beta-adrenoceptors than alpha-adrenoceptors in the rat pulmonary vascular bed and that beta-adrenoceptors may regulate the vascular tone of the rat pulmonary circulation.
Serotonin (5-HT) and some alpha-agonists induced a marked contraction of ring segments of the rat pulmonary artery. Phenylephrine and 5-HT caused maximum contractions in the artery amounting to 91% and 66%, respectively, of the maximum effect of noradrenaline. Clonidine failed to induce contractions in the artery. The alpha 1-adrenoceptor blocker prazosin (1 X 10(-6)M) and alpha 2-adrenoceptor blocker yohimbine (5 X 10(-7)M) did not antagonize 5-HT-induced contractions. However 5-HT2 receptor antagonists ketanserin (3 X 10(-9)-1 X 10(-7)M), mianserin (3 X 10(-9)-1 X 10(-7)M) and pizotifen (3 X 10(-9)-1 X 10(-7)M) competitively antagonized 5-HT-induced contractions in the tissue studied, whereas the antagonist methysergide (5 X 10(-10)-1 X 10(-7)M) caused a noncompetitive antagonism. The pA2 values for ketanserin (8.98), mianserin (9.1) and pizotifen (9.14) against 5-HT were not different from the values obtained in other tissues which were shown to contain 5-HT2 receptors. The results suggest that 5-HT receptors in rat main pulmonary artery are of the 5-HT2 subtype.
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Female rats were allowed to consume ethanol during gestation and lactation, and brain polyphosphoinositides of the 21-day-old pups were quantified. Ethanol intake prevented the disappearance of the metabolically labile pools of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bis-phosphate, which are rapidly degraded in the control group. In contrast, preweaning undernutrition left the size of these pools virtually unchanged, indicating a differential effect of the two nutritional regimens.
Polyphosphoinositides in rat brain exist in two forms: the metabolically active form that is readily attacked by the polyphosphoinositide phosphohydrolases, and the inert form that is attacked by the enzymes at a slower rate. The two pools continue to increase even during the postweaning period, suggesting a role in glial as well as myelin development apart from their role in neurons.
Metabolically inert polyphosphoinositides seem to play an important role in the structural development of neurons, glia, and myelin. The metabolically active pool of PhIpp appears to be important for the functional development of glia and myelin during the postweaning period, whereas PhIp seems to be more important for the functional development of neurons during the preweaning period. Neonatal undernutrition reduces the concentrations of structural polyphosphoinositides and metabolic PhIp while metabolic PhIpp remains unaltered. These effects can be reversed by postweaning nutritional rehabilitation. A continued postweaning protein deficiency of neonatally undernourished rats affects structural PhIpp more than PhIp. Metabolically active PhIpp is drastically reduced.
Presynaptic inhibitory effects of noradrenaline, clonidine and fentanyl on twitch contractions evoked by transmural electrical stimulation were investigated in guinea-pig common bile duct (CBD). Antagonism of the response to fentanyl by naloxone and to noradrenaline and clonidine by yohimbine confirmed the involvement of presynaptic opiate and alpha 2-adrenoceptors respectively. Clonidine caused desensitization of presynaptic alpha 2-adrenoceptors. No cross desensitization between clonidine and fentanyl was observed. Furthermore, partial agonistic activity of clonidine at presynaptic alpha 2-adrenoceptors was also observed by the antagonism of noradrenaline response in this preparation.
The effects of serotonin (5-HT) on the perfusion pressure of the isolated rat lung was investigated at 2 different temperatures (37 degrees C and 15 degrees C). 5-HT (1-30 micrograms) increased the perfusion pressure dose-dependently and a biphasic vasoconstrictor response appeared with the doses of 3-30 micrograms at 37 degrees C. Both phases were only blocked by methysergide (5 X 10(-10) M) among the 5-HT antagonists tested. At 15 degrees C, 5-HT (0.3-30 micrograms) elicited a similar response but the second phase appeared with the higher doses of the agonist compared to that at 37 degrees C. The initial phase, which was significantly higher than that at 37 degrees C, was antagonized by ketanserin, mianserin, pizotifen and methysergide in a noncompetitive manner. The order of potencies of the 4 serotonergic antagonists was compared with their affinity for central 5-HT receptors. The results led us to conclude that receptors mediating the initial phase of the vasoconstrictor response to 5-HT at 15 degrees C are neither of the 5-HT1 nor of the 5-HT2 type, but are 5-HT1 ones at 37 degrees C in the rat pulmonary vascular bed.