Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. None of the genes responsible for essential hypertension has been identified. Recent work in genetically hypertensive rats has shown linkage of blood pressure with alleles of the renin gene. Since the renin gene is a member of a conserved synteny group that in humans spans chromosome 1q21.3-32.3 and includes the gene for antithrombin III (AT3), we used linkage studies to examine the relationship between alleles of AT3 and hypertension in a family having 10 affected members. 2. From the lod score obtained at a recombination fraction of zero the odds for linkage of AT3 and hypertension in this family were calculated as 6:1 in favour of linkage. This result provides grounds for further examination of the possible role of the 1q23 locus in the aetiology of essential hypertension.
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PMID:A locus on the long arm of chromosome 1 as a possible cause of essential hypertension. 167 20

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, lambda HR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 PstI RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by chi 2 analysis (P greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension. 168 42

Although one large family with hereditary motor and sensory neuropathy (HMSN) type I that showed linkage to the Duffy blood group (FY) on chromosome 1 has previously been reported, we have failed to find evidence for such linkage after examining 14 markers from chromosome 1 in 12 pedigrees. We have excluded linkage between HMSN I and FY up to theta = 0.15 (lod = -3.01) and also between HMSN I and markers flanking FY; amylase (AMY), polymorphic urinary mucin (PUM), serum amyloid protein (APCS), and alpha-spectrin (SPTA). We have excluded HMSN I from 70 cM around this linkage group. Other markers examined were MS1, oncogene L-myc (MYCL), beta-subunit of nerve growth factor (NGFB), oncogene N-ras (NRAS), glucocerebrosidase (GBA), apolipoprotein AII (APOA2), antithrombin III (AT3), renin (REN), and MS32. These cover both the long and the short arms of chromosome 1 in addition to the centromeric region and yielded no evidence of linkage to HMSN I. Two-point lod scores between these markers are also presented. It is possible that there are two or more loci for HMSN I and it will be necessary to obtain significant lod scores from individual families to resolve this issue. This is increasingly possible now that hypervariable genetic markers such as PUM are available.
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PMID:Absence of linkage of hereditary motor and sensory neuropathy type I to chromosome 1 markers. 273 79

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers--Duffy (Fy), antithrombin III (AT3), renin (REN), beta-nerve growth factor (NGFB), and salivary amylase (AMY1)--in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate the possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene.
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PMID:Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I. 289 83

Fifteen HMSN families with 218 members and documented male-to-male transmission and slow motor nerve conduction velocities were informative for linkage to Duffy blood group (Fy), antithrombin III cDNA probe (AT3) and renin (REN). Our data support linkage to Fy in 8 families (lod score = 2.45 at theta = 0) consistent with HMSN type IB. Linkage to AT3 (lod score = 1.28 at theta = 0) and linkage of Fy to AT3 (lod score = 1.61 at theta = 0) is also supported in 3 of the 8 original families. Linkage to REN (lod score = 0.78 at theta = 0), linkage of Fy to REN (lod score = 0.89 at theta = 0), and linkage of AT3 to REN (lod score = 0.88 at theta = 0) is supported in only 2 of the 8 original families. Linkage to Fy was rejected in seven families, consistent with HMSN type IA (lod score = -4.34 at theta = 0.05). Linkage to AT3 was rejected in 12 families (lod score = -9.52 at theta = 0.05). Linkage to REN was rejected in 13 families (lod score = -11.07 at theta = 0.05). Our data provide support for the concept of genetic heterogeneity in CMT hypertrophic neuropathy (HMSN type I). The linkage of HMSN type IB to Fy seems to be tighter than to AT3 and REN, strongly suggesting the mapping of HMSN type IB locus on the proximal part of the long arm of chromosome 1, close to the centromere.
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PMID:Linkage analysis of Charcot-Marie-Tooth neuropathy (HMSN type I). 330 18

This review summarizes emerging evidence that supports the notion of a separate brain renin-angiotensin system (RAS) complete with the necessary precursors and enzymes for the formation and degradation of biologically active forms of angiotensins, and several binding subtypes that may mediate their diverse functions. Of these subtypes the most is known about the AT1 site which preferentially binds angiotensin II (AII) and angiotensin III (AIII). The AT1 site appears to mediate the classic angiotensin responses concerned with body water balance and the maintenance of blood pressure. Less is known about the AT2 site which also binds AII and AIII and may play a role in vascular growth. Recently, an AT3 site was discovered in cultured neoblastoma cells, and an AT4 site which preferentially binds AII(3-8), a fragment of AII now referred to as angiotensin IV (AIV). The AT4 site has been implicated in memory acquisition and retrieval, and the regulation of blood flow. In addition to the more well-studied functions of the brain RAS, we review additional less well investigated responses including regulation of cellular function, the modulation of sensory and motor systems, long term potentiation, and stress related mechanisms. Although the receptor subtypes responsible for mediating these physiologies and behaviors have not been definitively identified research efforts are ongoing. We also suggest potential contributions by the RAS to clinically relevant syndromes such as dysfunctions in the regulation of blood flow and ischemia, changes in cognitive affect and memory in clinical depressed and Alzheimer's patients, and angiotensin's contribution to alcohol consumption.
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PMID:Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. 817 Jun 22

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.
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PMID:Angiotensin II--receptor subtypes characterization and pathophysiological implications. 864 21

Since renin catalyses the first and rate-limiting step of the renin-angiotensin system (RAS) cascade, interruption of the generation of angiotensin II (Ang II) by renin inhibitors at this highly specific initial step of the cascade has long been a therapeutic goal. The early development of renin inhibitors was hampered by problems with bioavailability and high costs of synthesis. However, more recently a potent non-peptidic inhibitor of renin, aliskiren, with acceptable oral bioavailability, has been synthesised. Aliskiren effectively reduces Ang II levels in normal volunteers and has been shown to lower blood pressure (BP) in patients with mild-to-moderate hypertension. Renin inhibitors would be expected to have similar, but not identical effects to those of the established RAS antagonists. Due to the lack of effective alternative enzyme pathways, blockade of Ang II production may be more effective with renin inhibition than with angiotensin-converting enzyme (ACE) inhibition. Furthermore, because renin has high specificity for only one substrate, angiotensinogen, side-effects would be expected to be less frequent. It is currently unclear whether blockade of Ang II type 1 (AT1) receptors, leaving other Ang II receptors (AT2, AT3 and AT4) unblocked, is preferable to the reduction in plasma and tissue Ang II levels achieved with either ACE or renin inhibition. Pharmacological suppression of the RAS, through ACE inhibition, or blockade of AT1, beta-adrenoceptor or mineralocorticoid receptors, has been proven to reduce morbidity and mortality in patients with hypertension, diabetes mellitus, atherosclerosis, heart failure and nephropathy. While, to date, aliskiren has only been shown to reduce BP, it appears likely that orally-active renin inhibitors could prove useful in the management of a wide range of cardiovascular pathologies.
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PMID:Potential of renin inhibition in cardiovascular disease. 1269 47

Near complete reabsorption of filtered amino acids is a main specialized transport function of the kidney proximal tubule. This evolutionary conserved task is carried out by a subset of luminal and basolateral transporters that together form the transcellular amino acid transport machinery similar to that of small intestine. A number of other amino acid transporters expressed in the basolateral membrane of proximal kidney tubule cells subserve either specialized metabolic functions, such as the production of ammonium, or are part of the cellular housekeeping equipment. A new finding is that the luminal Na(+)-dependent neutral amino acid transporters of the SLC6 family require an associated protein for their surface expression as shown for the Hartnup transporter B(0)AT1 (SLC6A19) and suggested for the L: -proline transporter SIT1 (IMINO(B), SLC6A20) and for B(0)AT3 (XT2, SLC6A18). This accessory subunit called collectrin (TMEM27) is homologous to the transmembrane anchor region of the renin-angiotensin system enzyme ACE2 that we have shown to function in small intestine as associated subunit of the luminal SLC6 transporters B(0)AT1 and SIT1. Some mutations of B(0)AT1 differentially interact with these accessory subunits, providing an explanation for differential intestinal phenotypes among Hartnup patients. The basolateral efflux of numerous amino acids from kidney tubular cells is mediated by heteromeric amino acid transporters that function as obligatory exchangers. Thus, other transporters within the same membrane need to mediate the net efflux of exchange substrates, controlling thereby the net basolateral amino transport and thus the intracellular amino acid concentration.
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PMID:Kidney amino acid transport. 1918 91