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This minireview is concerned with a re-examination of the locus of action and the possible peripheral mechanisms involved in the gastrointestinal (GI) stimulant effects of metoclopramide. Such a re-evaluation is opportune given the increasing use of this drug in the therapy of certain GI tract disorders. To provide an orientation on this subject the location in the GI tract and function of several relevant receptor types have been reviewed. In the past metoclopramide has been reported to enhance contractions of a variety of GI preparations to electrical stimulation, acetylcholine, carbachol and ganglion stimulants, to inhibit responses to alpha 2-adrenoreceptor agonists and 5-hydroxytryptamine, as well as blocking those to dopamine. Also in such preparations metoclopramide facilitates the release of acetylcholine to transmural stimulation. One important question is whether this effect is mediated via a specific prejunctional receptor. In this respect 2 suggestions have been made. Firstly that the drug may act as a preferential, prejunctional muscarinic antagonist thus inhibiting the negative feedback inhibition of acetylcholine release and secondly that metoclopramide may be a prejunctional agonist (partial) at 5-hydroxy-tryptamine receptors. Although the latter possibility appears most tenable at present, the involvement of a specific receptor remains to be confirmed. The important finding that dopamine receptors are probably not involved in the local stimulant effects of metoclopramide has important implications for future research orientated towards the discovery of a new generation of GI drugs lacking the side effects associated with central dopamine receptor blockade. Several compounds (cinitapride, BRL 20627A and cisapride) are now in the early stages of clinical evaluation. 相似文献
773.
Preparation of chloroplast DNA from pea plastids isolated in a medium of high ionic strength 总被引:8,自引:0,他引:8
A simple, rapid, and inexpensive method for the preparation and purification of chloroplast DNA (cpDNA) from pea has been developed. The crucial step is the isolation of chloroplasts in a medium of high ionic strength (I congruent equal to 1.40 M). CpDNA from pea prepared according to this method has successfully been used for restriction enzyme mapping, Southern transfers, and cloning. 相似文献
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Jeroen M. G. Stevens Hilde Vervaecke Han de Vries Linda van Elsacker 《International journal of primatology》2007,28(6):1417-1430
Bonobos have a reputation as a female-dominated and egalitarian species. We examined the 2 aspects of dominance in 6 captive
bonobo groups. Females do not consistently evoke submission from all males in all contexts. Though females occupy the highest-ranking
positions in the dominance hierarchy, there are in each group males that obtain rather high ranks and are able to dominate
≥1 female. Thus female dominance is not complete and hierarchies can be better described as nonexclusive female dominance.
We studied egalitarianism by measuring linearity and steepness of dominance hierarchies. The hierarchies of all groups are
highly linear. Hierarchies among males are steeper than among females. On average, male bonobos are more despotic than females,
but females too can have despotic relations, both with other females and with males. Hence one can call bonobos in captivity
semidespotic rather than egalitarian. 相似文献
777.
Inhibition of prostaglandin F 2a or LH induced luteolysis in the pseudopregnant rabbit by 17 -estradiol 总被引:1,自引:0,他引:1
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E Shistik T Keren-Raifman G H Idelson Y Blumenstein N Dascal T Ivanina 《The Journal of biological chemistry》1999,274(44):31145-31149
The first 46 amino acids (aa) of the N terminus of the rabbit heart (RH) L-type cardiac Ca(2+) channel alpha(1C) subunit are crucial for the stimulating action of protein kinase C (PKC) and also hinder channel gating (Shistik, E., Ivanina, T., Blumenstein, Y., and Dascal, N. (1998) J. Biol. Chem. 273, 17901-17909). The mechanism of PKC action and the location of the PKC target site are not known. Moreover, uncertainties in the genomic sequence of the N-terminal region of alpha(1C) leave open the question of the presence of RH-type N terminus in L-type channels in mammalian tissues. Here, we demonstrate the presence of alpha(1C) protein containing an RH-type initial N-terminal segment in rat heart and brain by using a newly prepared polyclonal antibody. Using deletion mutants of alpha(1C) expressed in Xenopus oocytes, we further narrowed down the part of the N terminus crucial for both inhibitory gating and for PKC effect to the first 20 amino acid residues, and we identify the first 5 aa as an important determinant of PKC action and of N-terminal effect on gating. The absence of serines and threonines in the first 5 aa and the absence of phosphorylation by PKC of a glutathione S-transferase-fusion protein containing the initial segment suggest that the effect of PKC does not arise through a direct phosphorylation of this segment. We propose that PKC acts by attenuating the inhibitory action of the N terminus via phosphorylation of a remote site, in the channel or in an auxiliary protein, that interacts with the initial segment of the N terminus. 相似文献
780.