[Effect of synthetic motilin on gastric motor activity in conscious dogs].
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Biomedical subjects
Publications and source records attributed to R Takayanagi.
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Gastric movements were monitored in five conscious dogs weighing 9 to 13 kg by extraluminal force transducers (EFTs) which were independently developed and constructed in our own laboratory. After chronically implanting EFTs both in the canine gastric body and antrum we succeeded in making continuous recordings of their movements over several days. Dogs fed once a day with regular meals showed a circadian rhythm which was divided into three phases; digestive, intermediate, and an interdigestive phase. The digestive phase, which continued for about 8 to 10 hours after feeding, was characterized by a lack of movement in the body and repetitive rhythmical contractions having a rather small amplitude in the antrum. The interdigestive phase was distinguished from other phases by a peculiar sequence of gastric movements (interdigestive contractions) which did not make their appearance until 16 hours after feeding. These interdigestive contractions were the highest amplitude contractions to occur in both the body and antrum during the day. They continued for 70 minutes and repetitively recurred after intervening quiet periods of about 22 minutes. The intermediate phase was the period interposed between the digestive and interdigestive phase.
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Gastrointestinal contractile activity from the lower esophageal sphincter to the terminal ileum in the conscious dogs was continuously recorded on a multi-channel polygraph for several weeks by means of chronically implanted strain gage force transducers. It was found that the 24-hour gastrointestinal motor activity consisted of the two different major patterns; the digestive and interdigestive patterns. The interdigestive motor activity was characterized by a cyclic recurring, caudad-moving band of strong contractions interrupted by long lasting motor quiescence. When one band of strong contractions reached the distal ileum, another developed in the LES, stomach and duodenum again and propagated in a caudad-direction. Such recycling episodes repeatedly occurred until the next meal. After ingestion of food, gastrointestinal motor activity was continous and such characteristic interdigestive patterns were not observed. Synthetic motilin, 0.1-2.7 mug/kg/hr, was assayed for its motor stimulating activity in the both states. In the digestive state, an i.v. infusion of motlin had no influence upon the motor activity even if the dose was increased up to 6.0 mug/kg/hr. On the other hand, when motilin was infused during the interdigestive state, it induced a pattern precisely like the naturally-occurring interdigestive contractions. Not only the naturally-occurring contractions but also motilin-induced contractions were strongly inhibited by the ingestion of food or an i.v. infusion of pentagastrin (0.2-1.8 mug/kg/hr). Duodenal acidification (0.1 N HC1, 3-16 ml/kg/hr) in the interdigestive state disturbed or inhibited the regular cycle of the natural contractions but was counteracted by exogenous i.v. infusion of motilin. These findings strongly suggest the view that the interdigestive gastrointestinal motor activity is at least in part regulated by circulating motilin concentration in the blood, however, its cyclic recurring, caudad propagating mechanism may be controlled in part by the nervous system. Motilin is the only substance known to be active during the interdigestive state and therefore may be called the interdigestive hormone.
The effect of intracerebroventricular (ICV) injection of atrial natriuretic factor (ANF) on drinking and pressor responses induced by centrally administered angiotensin II (AII) was examined in the rat. The ICV injection of ANF attenuated water intake induced by AII or 48-hr water deprivation. In contrast, ANF did not affect AII-induced pressor responses. The ICV injection of ANF did not cause recognizable change in blood pressure in spontaneously hypertensive rats or Wistar-Kyoto rats. These results suggested that ANF in the brain is involved in the central control of water intake. Brain ANF may be considered as a selective antagonist of the dipsogenic effect of AII but not its pressor effect.
Ad4BP (or SF-1) is an essential transcriptional factor for steroidogenesis as well as for the development of the reproductive axis. We elucidated the structure of the human Ad4BP gene. The spliced variants of Ad4BP gene, ELP1 and ELP2 in mice, are unlikely to be present in humans since the analysis of the human gene revealed an in frame stop codon, 36-bp before the first ATG of Ad4BP. The promoter sequence of human Ad4BP, upstream of non-coding exon 1 was highly conserved, and E-box was also found to be essential for the transcription of human Ad4BP gene. During the process of the human Ad4BP gene cloning, we happened to obtain an Ad4BP-related gene, FTZ-F1beta which also belongs to the nuclear receptor family. We revealed cDNA structures of rat FTZ-F1beta, and found that rat has at least two types of FTZ-F1beta isoforms, which differ only by 21 amino acids length in the A/B domain. The tissue distributions of FTZ-F1beta in rat examined by RT-PCR, was found to be abundant in liver, pancreas, and gastrointestinal tracts. These results suggest that the physiological significance of FTZ-F1beta is different from that of Ad4BP.
The atrium of the heart contains peptides, termed atrial natriuretic factors ( ANFs ), diuretic and smooth-muscle-relaxing activities. In view of its potent effects on salt metabolism in the kidney and on vascular smooth muscle, ANF is considered to play an important part in the control of fluid volume and vascular function. Several different ANF peptides varying in size have been isolated and their amino acid sequences determined. Analysis of the sequences of the peptides suggests that they are derived by proteolysis from the same precursor. To examine this hypothesis, we have cloned cDNAs of the ANF precursor using rat atrial mRNA, determined its nucleotide sequence and deduced its amino acid sequence. The ANF precursor consists of 152 amino acid residues including a putative signal peptide sequence. This sequence contains the amino acid sequences of all the ANF peptides reported to date.