[Contribution to problems of screening of hypertonics at productive age (author's transl)].
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Biomedical subjects
Publications and source records attributed to O Kadlec.
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The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin on the release of acetylcholine (ACh), noradrenaline (NA) and prostaglandin-like substances from the isolated guinea-pig ileum and its longitudinal muscle-myenteric plexus preparation were investigated. The output of ACh and PGs was determined by a bioassay and the output of NA by an isotope technique. The output of ACh, both resting and stimulated, was decreased by indomethacin (1 micron) especially after a longer exposure. The output of ACh was increased by PGE2 (6 nM) but not by PGF2alpha. This increase was inversely related to the initial level of ACh output; thus, it was marked only in the preparations with low initial output of ACh. Prostaglandin-like substances released from the ileum were mainly of the E type and their output only partially correlated with contractions and with the output of ACh. The stimulated outflow of NA at a frequency of 5 Hz was increased by indomethacin (50 micron) and decreased by PGE2 (30 nM). PGF2alpha had no effect. These results suggest that PGE2 might act physiologically as a modulator of cholinergic transmission whereas its effect on adrenergic transmission could be of a pharmacological nature.
Electrical and mechanical activity of smooth muscle of the guinea-pig caecum was recorded by means of the sucrose-gap technique. The responses of longitudinal and circular smooth muscle to acetycholine were differently affected by changes of extracellular calcium concentration (0.8, 2.5 and 7.5 mM). The contractions of both preparations were depressed at high Ca++ concentrations, whereas at low Ca++ concentrations only contractions of the circular smooth muscle were augmented. The stimulatory effect of acetylcholine was decreased by papaverine in both preparations at all three concentrations of Ca++. This inhibition was the greater the lower the concentration of extracellular Ca++ and this process was more pronounced in the circular muscle. The ability of papaverine to counteract the effect of lowered concentrations of extracellular Ca++ on membrane excitability may well explain its inhibitory effect upon intestinal smooth muscle.
Responses of the longitudinal and circular smooth muscle of the guinea-pig caecum were studied in media with different concentrations of extracellular calcium. A sucrose-gap method was used to record the electrical and mechanical parameters of smooth muscle activity. In the longitudinal smooth muscle no difference in the action of PGF2alpha and PGE1 was seen at low (0.8 mM), Normal (2.5 mM) or high (7.5 mM) concentrations of Ca2+. Both PG's stimulated the longitudinal strip and the action of acetylcholine at normal Ca2+ concentration was slightly inhibited immediately after the superfusion with the PG's and augmented thereafter. In the circular strip no significant difference between the stimulatory effect of PGF2alpha, and PGE1 in low and high Ca2+ solution was found. However at 2.5 mM Ca2+ PGF2alpha evoked much greater stimulation of the circular strip than did PGE1. After the end of the superfusion with either PG the effect of acetylcholine was inhibited by either PG at low Ca2+ level and potentiated at high Ca2+ level the effect of acetylcholine was inhibited by PGE1 but not by PGF2alpha. Thus, the effects of PGF2alpha and PGE1 on the circular smooth muscle differed from each other in their dependence on the concentration of extracellular calcium.
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1 The role of prostaglandins in contractions of the guinea-pig ileum evoked either directly by acetylcholine or indirectly by angiotensin and by coaxial stimulation has been investigated.2 Prostaglandin E(2) in low concentration (6 nM) slightly augmented both types of contraction. Indomethacin, an inhibitor of prostaglandin synthesis, markedly reduced the indirectly evoked contractions but did not affect contractions in response to acetylcholine. The addition of prostaglandin E(2) to the preparation treated previously with indomethacin restored the effect of indirect stimulation.3 The pretreatment of the preparation with guanethidine or alpha-methyl-p-tyrosine prevented the inhibitory effect of indomethacin on indirectly evoked contractions. Prostaglandin E(2) addition to such preparations considerably augmented both types of contraction.4 The stimulation of non-cholinergic, non-adrenergic inhibitory nerves in the taenia coli and ileum preparations evoked hyperpolarization and relaxation of the preparations followed by action potentials and contraction. These responses were not changed by indomethacin pretreatment and prostaglandin E(2), but rebound contraction was sometimes augmented by the prostaglandin.5 Two mechanisms for the effects of prostaglandin E(2) are suggested: a direct effect on smooth muscle, and an indirect action through the sympathetic nerves which by release of noradrenaline affect the acetylcholine release from parasympathetic nerve endings.
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