ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3622998

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The cellular and molecular mechanisms underlying smooth muscle contraction are reviewed in the light of recent studies of smooth muscle ultrastructure and of the role of polyphosphoinositide turnover and protein kinase C function in smooth muscle contraction. A new model of smooth muscle contraction is proposed that differs radically from accepted views, particularly the latch bridge hypothesis, in terms of both Ca2+messenger function and the molecular events underlying this process. A coordinate fibrillar domain model of contraction is proposed in which the initial and sustained phases of contraction are mediated by different cellular and molecular events. The initial phase of response is mediated by a rise in [Ca2+]cand the resulting calmodulin‐dependent activation of both myosin light chain kinase and the dissociation of caldesmon from the actin‐caldesmon‐tropomyosin‐myosin fibrillar domain. These events lead to an interaction between actin and the phosphorylated light chains of myosin just as in previous models. However, this initial phase is followed by a sustained phase in which a rise in [Ca2+]smstimulates the plasma membrane‐associated, Ca2+‐sensitive form of protein kinase C that results in the phosphorylation of both structural and regulatory components of the filamin‐actin‐desmin fibrillar domain. These events underlie the tonic phase of contraction.— Rasmussen, H.; Takuwa, Y.; Park, S. Protein kinase C in the regulation of smooth muscle contraction.FASEB J.1: 177‐185; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3040504

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The leukotrienes (LTs) are 5‐lipoxygenase metabolites of arachidonic acid. The synthesis and release of LTs have been demonstrated in many cells and organs, and LTs are considered to be normal products of continuous metabolism of arachidonic acid. However, although evidence in favor of a critical role for LTs in regulation of physiological functions is still scarce, a growing body of evidence suggests a role for LTs in mediation of several pathophysiological processes such as generalized or local immune reactions, inflammation, asthma, shock, and trauma. LTs have been shown to have potent actions on many essential organs and systems, including the cardiovascular system (heart, blood vessels, microcirculation), the pulmonary system (lung, airways), the central nervous system (neural, glial, and vascular elements), the gastrointestinal tract, and the immune system. In these organs the effects of LTs are mediated by specific LT receptors. Identification of LTs and characterization of their regional and systemic pathological effects, together with characterization of their receptors and elucidation of their structure‐activity relationships, are fundamental to developing LT antagonists or synthesis inhibitors that might prevent or reverse LT‐dependent reactions. Preliminary reports have already shown that such pharmacological agents ameliorate some aspects of disease processes in experimental animals as well as in humans. In this brief review we intend to highlight the evidence that implicates LTs in normal physiological functions as well as in disease processes.— Feuerstein, G.; Hallenbeck, J. M. Leukotrienes in health and disease.FASEB J.1: 186‐192; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3040505

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The sympathetic neuroeffector system in the mammalian cerebral circulation has a number of distinctive features that reflect its specialized role in this vascular bed:1) there is limited α‐adrenoceptor‐mediated contraction in large vessles that becomes progressively less important with branching;2) contraction is limited by receptor number; small branches often seem to have no functional α adrenoceptors;3) adrenoceptor affinity for norepinephrine is low and so is sensitivity; and4) the dominant α‐adrenoceptor subtype differs in different species and may have unique characteristics in some. There is a mechanism of non‐α‐adrenoceptor‐mediated contraction involving low‐affinity receptor sites—extraceptors—activated by sympathetic nerves. The pig has a seemingly atypical sympathetic mechanism. On the basis of current information the sympathetic neuroeffector mechanisms of the rabbit seem most clearly related to the human. The size, pattern, and distribution of sympathetic control suggest that the role of the sympathetic nerves is to protect the smaller pial arteries against the consequences of sudden increases in sympathetic adrenal discharge. It is not an important mechanism of controlling cerebral blood flow.— Bevan, J. A.; Duckworth, J.; Laher, I.; Oriowo, M. A.; McPherson, G. A.; Bevan, R. D. Sympathetic control of cerebral arteries: specialization in receptor type, reserve, affinity, and distribution.FASEB J.1: 193‐198; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.2887477

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

The thesis is advanced that immune responses to intraocular antigens are unique and highly specialized. Anterior chamber‐associated immune deviation (ACAID) is the term used to identify this specialized response, which consists of selectively impaired immunity of the delayed hypersensitivity (DH) type coexistent with intact humoral immunity and priming of cytotoxic T cell activity. Induction of T cell suppression, which is partly responsible for ACAID, interferes with expression of DH within the eye as well as systemically. It is proposed that the ability of the eye to make a compromise with the immune system and thereby arrange for the selective suppression of delayed hypersensitivity results from the need to avoid intraocular inflammatory reactions that are intense and productive of nonspecific “innocent bystander” injury. When reactions of this type occur within the eye, the visual axis is disrupted, and vision is destroyed. However, avoidance of DH may have deleterious consequences both for the eye and for the host. The impact of ACAID is discussed with regard to the distinctive patterns of ocular disease produced experimentally in mice by melanoma cells and by herpes simplex virus type 1.— Streilein, J. W. Immune regulation and the eye: a dangerous compromise.FASEB J.1: 199‐208; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.2957263

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Although the serum protein α1‐acid glycoprotein (AGP) or orosomucoid has been extensively studied, its relationships with other proteins have been controversial and its precise physiological function has remained unclear. It is shown here that AGP is significantly similar in amino acid sequence and in the locations of introns in its structural gene to members of a protein superfamily that includes serum retinol‐binding protein (RBP), β‐lactoglobulin (LG), α2u‐globulin, and protein HC (α1‐microglobulin). The view that the three‐dimensional structure of AGP is closely similar to the published structures of RBP and LG is supported by its homology with these proteins, similarities in disulfide bond arrangements, and its secondary structure profile, predicted from the amino acid sequence. The relationship of AGP with this particular protein family indicates that its well‐characterized ability to bind lipophilic drugs and certain steroids is a reflection of its true biological role. It is proposed that AGP and the other members of this extensive group of proteins should be designated lipocalins to reflect a common ability to bind lipophiles by enclosure within their structures in a manner that minimizes solvent contact.—Pervaiz, S.; Brew, K. Homology and structure‐function correlations between α1‐acid glycoprotein and serum retinol‐binding protein and its relatives.FASEB J.1: 209‐214; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3622999

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Rat glomerular mesangial cell monolayers loaded with the fluorescent probe fura‐2 responded to exogenous platelet‐activating factor (PAF) with a rapid increase in cytosolic free calcium concentration ([Ca2+]i). PAF‐induced [CA2+]itransients consisted of a dose‐dependent phasic peak response followed by a sustained tonic phase of increased [Ca24]i. Chelation of extracellular calcium with EGTA suppressed the tonic phase of increased [Ca2+]ibut did not affect the phasic peak response. This suggests two mechanisms for the elevation of [Ca2+]i: a transient mobilization from intracellular stores and an enhanced calcium influx across the plasma membrane, possibly mediated by receptor‐operated channels. Lyso‐PAF had no effect on basal [Ca2+]i, and the PAF‐receptor antagonist L652,731 selectively inhibited responses to PAF. PAF‐stimulated mesangial cells displayed homologous desensitization to reexposure to PAF while still being responsive to other calcium‐mobilizing agonists. Preincubation of cells with the protein kinase C (PKC) activator phorbol myristate acetate diminished the PAF‐induced [Ca2+]itransient, suggesting a regulatory role for PKC in PAF‐activation of mesangial cells. An increase in [Ca2+]i, as a result of receptor‐linked activation of phospholipase C, may mediate PAF‐induced hemodynamic and inflammatory events in renal glomeruli.— Kester, M.; Menè, P.; Dubyak, G. R.; Dunn, M. J. Elevation of cytosolic free calcium by platelet‐activating factor in cultured rat mesangial cells.FASEB J.1: 215‐219; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.2442057

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of γ‐glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdC12. Mice pretreated with a sublethal dose of Cd2+to induce metallothionein synthesis were not sensitized to Cd2+by buthionine sulfoximine. Mice sensitized to Cd2+by buthionine sulfoximine were protected against a lethal dose of Cd2+by glutathione mono isopropyl ester (l‐γ‐glutamyl‐l‐cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+toxicity, and that this tripeptide provides a first line of defense against Cd2+before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione‐dependent biological phenomena.— Singhal, R. K.; Anderson, M. E.; Meister, A. Glutathione, a first line of defense against cadmium toxicity.FASEB J.1: 220‐223; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.2887478

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Epidermal growth factor (EGF) produces uterine contractions in tissues removed from immature and adult rats. EGF produces both an increase in resting tone and the development of rhythmic contractions, and this effect is abolished by treatment with antibodies against EGF. The ED50for this response is observed at an EGF concentration of 3.5 nm. This in vitro effect of EGF requires treatment of the animals in vivo with estradiol for 24 h before removal of uterine tissue. This effect of estradiol does not appear to be due solely to an induction of tissue EGF receptors. These results demonstrate a new activity of EGF and suggest a previously unrecognized function for this peptide growth factor.— Gardner, R. M.; Lingham, R. B.; Stancel, G. M. Contractions of the isolated uterus stimulated by epidermal growth factor.FASEB J.1: 224‐228; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3497834

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

Using high‐pressure liquid chromatography (HPLC) and gas‐liquid chromatography/mass spectrometry (GLC/MS), we have confirmed the existence of several sialic acid modifications in the adult rat and human colon. The majorO‐acetylated sialic acid in both species is 9‐O‐acetyl‐N‐acetylneuraminic acid;N‐glycolylneuraminic acid is a major component of the adult rat colon. Both of these major modifications were found to be developmentally regulated during the perinatal period in the rat. TheN‐glycolyl modification is present prenatally and disappears rapidly in the postnatal period. It reappears in the preweanling period, reaching levels at weaning comparable to those found prenatally. In contrast, the 9‐O‐acetyl modification is very low prenatally, and undergoes a marked increase shortly after birth in both the rat and human colon. The difference in the kinetics of appearance of the two modifications suggests that they are independently regulated. Regulation of these modifications seems to be influenced by exposure to bacterial by‐products or environmental stimuli. TheN‐glycolyl modification in the rat colon reappeared at weaning, a time of major change in enteral colonic substances. Spontaneously aborted human fetuses, including three with intrauterine infection at 27, 33, and 35 wk of gestation, showed adult levels ofO‐acetylation in colonic tissue. Also, althoughO‐acetylation in freshly isolated colon tumor specimens was only somewhat lower than that in the adult normal colon, all established colon cancer cell lines studied showed minimalO‐acetylation.— Muchmore, E. A.; Varki, N. M.; Fukuda, M.; Varki, A. Developmental regulation of sialic acid modifications in rat and human colon.FASEB J.1: 229‐235; 1987.

ISSN:0892-6638    

DOI:10.1096/fasebj.1.3.3623000

出版商:Wiley    

年代:1987

数据来源: WILEY