Substance P: regional distribution and specific binding to synaptic membranes in rabbit central nervous system.
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Biomedical subjects
Publications and source records attributed to H Yajima.
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Effect of methionine-, leucine-enkephalin (met-, leu-enkephalin) and substance P on the transmission in mouse vas deferens was studied. Both met- and leu-enkephalin inhibited electrically induced contraction of vas deferens at 10(-8)-10(7) M, met-enkephalin being 1.4 times more active than leu-enkephalin. Nalorphine (10(-6) M) antagonized these effects. Substance P (10(-9)-10(-7) M) had no effect on the contraction. Met- and leu-enkephalin (10(-7)-10(-5) M) decreased the high potassium induced [3H]-norepinephrine release from vas deferens, while substance P (10(-6) M) significantly increased it. Nalorphine (10(-5) M) reversed the inhibitory effect of met-enkephalin. These results indicate that these peptides modify the transmission of sympathetic nerve in mouse vas deferens.
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We have studied the effect of Yajima's synthetic motilin on the lower esophageal sphincter (LES) of the opossum and compared its potency to that of gastrin and its interaction with secretin. Dose-response curves for the LES were constructed from the intravenous bolus injection of graded doses of motilin and gastrin alone and motilin given against a background infusion of secretin. The smallest dose of motilin that elicited a significant response was 0.05 microng/kg, and the highest response was observed with the highest dose used in this study (1.0 microng/kg). Over a wide dose range, both motilin and gastrin were found to be equally potent in stimulating the LES of the opposum, and secretin caused inhibition of the LES pressure to motilin. Therefore, we conclude that (1) motilin is a potent stimulant of the LES; (2) this response is dose dependent; (3) motilin's potency is similar to that of gastrin; and (4) secretin counteracts the effect of motilin on the LES.
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Crude mitochondrial P2 fractions from bovine hypothalamus and substantia nigra, slices from rabbit spinal cord and mesencephalon and glial fractions from rabbit brain were incubated with [3H]-substance P and the uptake was measured and compared with those for 5-HT and GABA. Substance P was to some extent taken up into the fractions but this uptake was neither temperature nor time dependent and the pellet/medium ratios were less than 1. Similar results were obtained in high potassium treated slices from rabbit mesencephalon. The rate of uptake for [3H]-substance P increased linearly in proportion to the medium concentration, suggesting a non-saturable binding. These results, together with our previous observations provide strong evidence that nerve terminals and glial cells lack a temperature sensitive, active uptake system capable of terminating transmitter action of substance P at the synapse.
The docosapeptide and the tritetracontapeptide corresponding to the entire amino acid sequence of porcine motilin and gastric inhibitory peptide were synthesized, and in addition, an unsulfated form of cholecystokinin-pancreozymin (CCK-PZ) was prepared to cast some light on the structure-activity relationships of these gastrointestinal hormones. In a series of motilin peptides, elimination of the pentapeptide from the amino terminus decreased the activity (in vitro contraction of rabbit duodenal muscle) to 1/250 of the whole molecule, and subsequent removal of the tripeptide Thr-Tyr-Gly resulted in the complete loss of its effects, In a series of gastric inhibitory peptides, two fragments corresponding to positions 1 to 28 and 26 to 43 were both inactive. However, the nonacosapeptide (15 to 43) retained one-fourth of the activity of the tritetracontapeptide (suppression of the gastric acid secretion stimulated by tetragastrin in Heidenhain pouch dogs). Synthetic [27-Tyr]CCK-PZ exhibited 1/250 of the activity of natural CCK-PZ (amylase release from rat pancreas). This compound was smoothly and efficiently labeled with 125I (specific activity 200 to 250 muc per mug).
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