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A Husain

Publications and source records attributed to A Husain.

At least 109 records · Page 6Linked to original sources
PubMed1988

Distribution of angiotensin-converting enzyme and angiotensin II-receptor binding sites in the rat ovary.

Recent reports of the presence of components of the renin-angiotensin system (RAS) in the mammalian ovary suggest that angiotensin II (Ang II) may be elaborated by this structure. In this study, angiotensin-converting enzyme (ACE), a key enzyme in the synthesis of Ang II, was identified enzymatically and localized to the germinal epithelium surrounding corpora lutea, granulosa cells of some--but not all--follicles, and blood vessels of the rat ovary using a potent and specific radiolabeled ACE inhibitor, 125I-351A. Follicles that bound 125I-351A also contained Ang II-receptor binding sites. Co-localization of RAS components to the follicular granulosa cells and the ability of Ang II to promote estrogen formation suggest that the ovarian RAS may promote follicular development and assertion of dominance.

Animals↗
PubMed1988

Angiotensin II: an intraovarian regulatory peptide.

Mammalian ovarian follicles contain the enzymes and prohormones necessary to elaborate the active octapeptide hormone angiotensin II. In the rat ovary, angiotensin II receptors are located primarily in the theca interna and granulosa cell layers of a discrete subpopulation of follicles. Angiotensin II stimulates both androgen and estrogen secretion from rat ovarian slices. These findings suggest an autocrine/paracrine role for angiotensin II in ovarian follicular development.

Androgens↗
PubMed1988

Evidence for selective expression of angiotensin II receptors on atretic follicles in the rat ovary: an autoradiographic study.

Ovarian angiotensin II (Ang II) receptors display a cyclical pattern of variation during the rat estrous cycle. Ang II receptors, estimated by the specific binding of the Ang II receptor antagonist [125I]iodo-[Sar1,Ile8] Ang II to ovarian membranes, were lowest at estrus [binding site density (Bmax) = 35 +/- 2 fmol/mg; binding site affinity (KD) = 2.0 +/- 0.2 nM] and highest at diestrus I (Bmax = 59 +/- 3 fmol/mg; KD = 1.6 +/- 0.1 nM). We have previously shown that Ang II receptors in the rat ovary predominantly exist on the granulosa cell layer of a subpopulation of follicles. Our present studies show that the Ang II receptor-containing follicles in the rat ovary are mainly atretic (approximately 80%) or show signs of early atresia (approximately 15%) during all stages of the estrous cycle. A small number of Ang II receptor-containing follicles were healthy (approximately 5%). In contrast to the Ang II receptor-containing follicles, the FSH receptor-containing follicles were predominantly healthy (greater than 90%). Follicles which contained both Ang II receptors and FSH receptors were mainly early atretic. Since Ang II receptor-containing follicles in the rat ovary were mainly atretic these studies suggest that in the rat Ang II may be a major factor in regulating the function of atretic ovarian follicles.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1988

Rat ovarian renin: characterization and changes during the estrous cycle.

To demonstrate the existence and help clarify the function of renin in the rat ovary, we have characterized rat ovarian renin and examined ovarian renin levels during different stages of the rat estrous cycle. We show that high concentrations of active renin are present in the rat ovary (2.9 ng angiotensin I/h/mg). Ovarian renin activity has a pH optimum of about 7.0 and is due to a glycosylated aspartyl protease with an apparent mol wt of 39,000. These properties of rat ovarian renin are identical to previously characterized rat kidney renin. In PMSG-treated immature and adult 5-day cycling rats, ovarian renin was increased about 2-fold at estrus. At all stages of the estrous cycle in the 5-day cycling rat, the ratio of active to inactive ovarian renin was about 3:1, whereas about 90% of the renin in plasma was inactive. In the hypophysectomized diethylstilbestrol-treated rat ovary, over 90% of active renin remained in the residual ovary after the granulosa cells had been expressed, suggesting a theca-interstitial localization for renin. These studies indicate that active renin exists in the rat ovary, that its levels are cyclically increased at estrus, and that this increase may be due to enhanced local production and activation of the renin precursor. These findings greatly strengthen the concept of a functional renin-angiotensin system in the rat ovary.

Ammonium Sulfate↗
PubMed1988

An immunoreactive form of erythrocyte protein 4.9 is present in non-erythroid cells.

Using immunoblots and an affinity-purified antibody prepared against human erythrocyte protein 4.9, we have demonstrated and quantified the presence of an immunoreactive form of this protein in avian and bovine brain and lens tissues, avian heart, as well as in human platelets and mammalian, avian, piscine, and amphibian erythrocytes. Both the 48 kDa and the 52 kDa variants were observed in human erythrocytes, whereas 50 kDa and 54 kDa immunoreactive forms were observed in human platelets. As reported for erythroid protein 4.9, platelet protein 4.9 was phosphorylated in response to treatment with phorbol ester. Bovine brain showed five cross-reactive polypeptides in the 47 to 52 kDa range while avian brain and avian and bovine lens exhibited predominantly a 49-kDa band. Cross-reactivity was not observed in a number of cell lines and tissues including leukocytes, liver, kidney, pancreas, and skeletal muscle. Immunofluorescence indicated that protein 4.9 was present in cortical fiber cells of avian lens and in neurons of avian cerebrum.

Animals↗
PubMed1987

Cellular organization of the brain renin-angiotensin system.

A model of intracellular Ang II formation (Figure 1) implies that angiotensinogen neurons exist and that CNS Ang II acts both as a neurotransmitter as well as a neurohormone. Such a mechanism is consistent with the immunocytochemical localization of a fraction of brain Ang II in neurosecretory vesicles. To date, several dozen peptide neurotransmitters and neurohormones have been studied. Those assigned to peptidergic systems follow the generalized pathway of biosynthesis shown in Figure 1. In peptidergic systems, a prohormone and all of its processing enzymes are synthesized in the rough endoplasmic reticulum of a cell and move into the Golgi apparatus (Figure 1: #1-3). In the Golgi the prohormone and processing enzymes are packaged into the same vesicle (#3). These secretory vesicles then migrate toward the plasma membrane, frequently via axonal or dendritic projections to terminals. Within these cytoplasmic vesicles and prior to release, the processing enzymes are activated (#4) and the prohormone enzymatically processed, yielding the active peptide (#5-6). Only then do the vesicles fuse with the plasma membrane (in a calcium-dependent process), releasing their contents (#7-8). Once released, the active peptide migrates across the extracellular space and interacts with specific cell surface receptors to initiate a response (#9). Finally, receptor-bound peptide degradation is initiated by receptor-mediated endocytosis (#10-11). For angiotensin peptides to be produced intracellularly, the cell must present only one secretory pathway for Golgi packaging of renin and angiotensinogen; otherwise current theories of protein sorting would predict that these two proteins would be segregated even if synthesized within the same cell. Small quantities of co-packaged renin and angiotensinogen occurring via "spill-over" between compartments seems an unsatisfactory process for a regulated hormone system. Figure 2, depicting an extracellular mechanism for producing Ang II in the brain, has also been proposed. The mechanism of extracellular angiotensin formation is consistent with the molecular information encoded within the component proteins, known mechanisms of protein secretio, well-defined systemic renin-angiotensin enzymatic cascades, and demonstration of all the components of the renin-angiotensin system in the extracellular compartments of the brain. This model (Figure 2) allows independently coordinated gene expression and synthesis of renin (#1R), angiotensinogen (#1A), and angiotensin-converting enzyme (# 1C) in the same or different cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin I↗
PubMed1987

Rat ovarian angiotensin II receptors. Characterization and coupling to estrogen secretion.

Angiotensin II receptor agonist (125I-angiotensin II) and antagonist (125I-[Sar1,Ile8]angiotensin II) bind in a specific and saturable manner to rat ovarian membranes. Agonist and antagonist binding affinity (KD approximately 0.5 nM) and the number of sites estimated (Bmax approximately 60 fmol/mg of protein) were similar. Dissociation of receptor-bound agonist was more rapid than the dissociation of receptor-bound antagonist, and agonist, but not antagonist, dissociation from the receptor was accelerated by GTP gamma S. A 0-150 mM increase in Na+ produced a 27% increase in the KD of agonist binding. Antagonist binding was not modified by Na+. These studies suggest that both agonist and antagonist identify putative angiotensin II receptors in the ovary but that the properties of agonist and antagonist binding are distinct. Angiotensin II antagonist binding sites are present on the granulosa cell layer of rat ovarian follicles (Speth, R. C., Bumpus, F. M., and Husain, A. (1986) Eur. J. Pharmacol. 130, 351-352). To determine the role of angiotensin II in ovarian function, we examined angiotensin II receptors and function during the onset of puberty. High affinity and low capacity angiotensin II receptors were present in ovaries from immature rats. After pregnant mare's serum gonadotropin induced ovulation in immature rats, antagonist binding to total ovarian membranes increased over 3-fold. In vitro incubation of peripubertal ovaries with 1 microM angiotensin II produced a stimulation of estrogen, but not progesterone, secretion. This steroidogenic effect of angiotensin II was most pronounced in the luteal phase of the estrus cycle. These studies point toward the involvement of angiotensin II in the regulation of ovarian function, possibly through modulation of follicular estrogen levels.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1987

Localization of angiotensin II receptors in ovarian follicles and the identification of angiotensin II in rat ovaries.

Specific, high-affinity (Kd approximately equal to 0.6 nM), and saturable (3.3 fmol/mg of tissue, wet weight) binding of 125I-labeled [Sar1,Ile8]angiotensin II to rat ovarian membranes was observed. Displacement of 125I-labeled [Sar1,Ile8]angiotensin II binding to rat ovarian membranes by angiotensin II analogs and fragments resembled the potency order of these compounds on angiotensin II receptors in other tissues: [Sar1,Ile8]angiotensin II greater than angiotensin II greater than des-Asp1-angiotensin II greater than angiotensin I greater than des-Asp1,Arg2-angiotensin II. Several unrelated peptides, including follicle-stimulating hormone at 10 microM, did not displace ovarian 125I-labeled [Sar1,Ile8]angiotensin II binding. Autoradiograms of 125I-labeled [Sar1,Ile8]angiotensin II binding to ovarian sections indicated that the angiotensin II receptor binding sites were localized exclusively to a subpopulation of follicles, occurring on the granulosa and theca interna cells. Other follicles were devoid of 125I-labeled [Sar1,Ile8]angiotensin II binding sites. Angiotensin II immunoreactive material was also identified in the ovary. The concentration of ovarian Ang II immunoreactivity was 8- to 75-fold greater than that of plasma, was not reduced in bilaterally nephrectomized rats, and was shown by high-pressure liquid chromatographic analysis to be the native angiotensin II octapeptide. The presence of angiotensin II and its receptor binding sites in the ovary suggests a role for angiotensin II as a regulator of ovarian function.

Angiotensin II↗
PubMed1987

Regulation of angiotensin II in rat adrenal gland.

Levels of angiotensin II immunoreactivity in the rat adrenal gland are over one hundredfold higher than those in plasma. It is unclear, however, whether the major source of adrenal angiotensin II immunoreactivity is intracellular synthesis by a local renin-angiotensin system, uptake by angiotensin II receptors, or both. Our studies show that angiotensin II immunoreactivity in the adrenal gland is predominantly attributable to angiotensin II (greater than 75%). Angiotensin III (16%) and other angiotensin II fragments are also present. The majority of angiotensin II immunoreactivity (73%), renin activity (73%), and angiotensin II receptor binding activity (66%) in the adrenal gland is located in the capsular glomerulosa cell layers. Dehydration produced by 2% NaCl imbibition decreased these activities in the capsular-glomerulosa. In the fasciculata-medullary regions of the adrenal gland, dehydration decreased renin activity but not angiotensin II immunoreactivity or angiotensin II receptor binding activity. Combined data from control and dehydrated rats showed a close correlation of the capsular-glomerulosa angiotensin II immunoreactivity with angiotensin II receptor binding activity (r = 0.94, p less than 0.001) and a weaker, nonsignificant correlation with renin activity (r = 0.66, p less than 0.1). In the fasciculata-medullary cell layers, no significant correlations were found between angiotensin II immunoreactivity and either renin or angiotensin II receptor binding activity. These data demonstrate that functionally distinct layers of the rat adrenal gland differentially regulate angiotensin II receptors and the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1986

Basal and potassium-evoked release of angiotensin II from the rat hypothalamus.

Although the protein components of the renin-angiotensin system have been localized in the brain, it remains to be established whether or not angiotensin II (Ang II) is generated locally and secreted into the interstitial fluid of the brain. We have addressed this issue in vitro by perifusing explants of the rat hypothalamo-neurohypophysial system (HNS) (5 explants per chamber, 37 degrees C) with Krebs solution at a rate of 1 ml/min. The release of Ang II immunoreactivity (Ang II-ir) and arginine vasopressin immunoreactivity (AVP-ir) in the medium was measured 3-5 h after HNS dissection and again after addition of potassium (K+) to the perifusate. Samples of the fluid perifusing the HNS were collected for 30-min intervals and concentrated using Sep-Pak C18 cartridges. Release of Ang II-ir was significantly increased during perifusion with 70 mM K+ (from 29 +/- 14 pg/30 min to 80 +/- 17 pg/30 min, P less than 0.01). This increase coincided with a dramatic rise in the release of AVP-ir (from 50 +/- 35 pg/30 min to values above 2000 pg/30 min). The associated release of Ang II-ir in response to depolarization by K+ is consistent with the hypothesis that Ang II can be secreted by neuronal elements of the brain, possibly via a regulated pathway.

Angiotensin II↗
PubMed1986

Purification of erythrocyte band 4.1 and other cytoskeletal components using hydroxyapatite-Ultrogel.

An improved method for purifying erythrocyte band 4.1, the protein which mediates the interaction between spectrin and actin, has been developed. The new procedure, using adsorption chromatography on hydroxylapatite crystals immobilized within a crosslinked agarose gel (HA-Ultrogel), is simple and reproducibly provides a high yield of band 4.1 which is essentially free of protein kinase. Other components eluted from the hydroxylapatite matrix include band 4.9, ankyrin, and a 35,000-Da polypeptide that appears to be glyceraldehyde-3-phosphate dehydrogenase that remains bound to the erythrocyte membrane in 150 mM NaCl.

Actins↗
PubMed1986

The association of acrylamide with proteins. The interpretation of fluorescence quenching experiments.

The association properties of acrylamide with a number of proteins in aqueous solution have been investigated by a fluorescence-quenching method previously used in micelles and lipid bilayers (Blatt, E., Chatelier, R.C. and Sawyer, W.H. (1984) Chem. Phys. Lett. 108, 397-400). At pH 7.0, acrylamide partitions between the bulk aqueous phase and the proteins, human serum albumin, monellin and ovalbumin. Comparison with an earlier method of analysis (Sikaris, K.A., Thulborn, K.A. and Sawyer, W.H. (1981) Chem. Phys. Lipids 29, 23-36) confirms the data quantitatively. For human serum albumin at pH 2.2, acrylamide associates according to both partition and binding processes. Equilibrium dialysis experiments performed for the latter system verify that acrylamide associates with proteins.

Acrylamide↗
PubMed1986

Cardiac angiosarcomas. A review and a case report.

Forty-five cases of cardiac angiosarcomas were reviewed, and the data were compared with those of a 1968 review of 41 other cases which revealed these tumors to be typically located within the right atrium as large symptomatic masses and to be rapidly fatal, with the diagnoses usually determined only at autopsy. The relationship of these tumors to Kaposi's sarcoma was also examined. The findings paralleled those of the previous review. Additionally, the following points emerged: With the aid of newer imaging techniques, localization, biopsy diagnosis and resection of the atrial tumors are now being achieved more often, with some improvement in survival. Like angiosarcomas of other organs, atrial angiosarcomas exhibit highly variable histologic patterns, which often overlap those of Kaposi's sarcoma, and may also present metastatic patterns simulating widespread Kaposi's sarcoma or malignant melanoma. In reported cases of classical, endemic, or epidemic Kaposi's sarcoma, cardiac lesions are uncommon and typically are small, asymptomatic, restricted to the epicardium/or pericardium and, thus, are clearly different, both clinically and pathologically, from the atrial tumor group. The justification for designating cases of the latter group as "primary cardiac Kaposi's sarcoma" is open to debate. A case report illustrates many of the above points.

Adult↗