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S Carrière

Publications and source records attributed to S Carrière.

At least 19 recordsLinked to original sources
PubMed2000

Catecholamines and angiotensinogen gene expression in kidney proximal tubular cells.

To investigate the molecular mechanism(s) of action of catecholamines on the expression of the angiotensinogen (ANG) gene in kidney proximal tubular cells, we used opossum kidney (OK) cells with a fusion gene containing the 5'-flanking regulatory sequence of the rat ANG gene fused with a human growth hormone (hGH) gene as a reporter, pOGH (rANG N-1498/+18), permanently integrated into their genomes. The level of expression of the ANG-GH fusion gene was quantified by the amount of immunoreactive-hGH (IR-hGH) secreted into the medium. The addition of norepinephrine (NE), isoproterenol (a beta1/beta2-adrenergic receptor (AR) agonist) and iodoclonidine (an alpha2-AR agonist) stimulated the expression of the ANG-GH fusion gene in a dose-dependent manner, whereas the addition of epinephrine and phenylephrine (alpha1-AR agonist) had no effect. The stimulatory effect of NE was blocked by the presence of propranolol (beta-AR blocker), atenolol (beta1-AR blocker), yohimbine (alpha2-AR blocker), Rp-cAMP (an inhibitor of cAMP-dependent protein kinase AI & AII) and staurosporine (an inhibitor of protein kinase C), but was not blocked by ICI 118, 551 (beta2-AR blocker) and prazosin (alpha1-AR blocker). The addition of a combination of isoproterenol and iodoclonidine or a combination of 8-Bromo-cAMP (8-Br-cAMP) and phorbol 12-myristate (PMA) synergistically stimulated the expression of the ANG-GH fusion gene as compared to the addition of isoproterenol, iodoclonidine, 8-Br-cAMP or PMA alone. Furthermore, the addition of NE, 8-Br-cAMP or PMA stimulated the expression of pOGH (rANG N-806/-779/-53/+18), a fusion gene containing the putative cAMP responsive element (CRE, ANG N-806/-779) upstream of the ANG promoter (ANG N-53/+18) in OK cells, but had no effect on the expression of fusion genes containing the mutant of the CRE. Gel mobility shift assays revealed that the ANG-CRE binds with the DNA-binding domain (bZIP254-327) of the cAMP-responsive binding protein (CREB). The binding of the labeled ANG-CRE to CREB (bZIP254-327) was displaced by unlabeled ANG-CRE and the CRE of the somatostatin gene but not by the mutants of the ANG-CRE. Finally, NE stimulated the phosphorylation of CREB in OK cells. These studies demonstrate that the molecular mechanism(s) of NE action on the expression of the ANG gene in OK cells may be mediated via both the PKA and PKC signalling pathways and via the phosphorylation of CREB. The phosphorylated CREB then interacts with the CRE in the 5'-flanking region of the ANG gene and subsequently stimulates the gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

beta-Adrenoceptors and dexamethasone synergistically stimulate the expression of the angiotensinogen gene in opossum kidney cells.

We transiently co-transfected opossom kidney (OK) cells with the plasmid containing the cDNA for beta 1-adrenoceptor (pBC-beta 1 AR) or beta 2-adrenoceptor (pBC-beta 2 AR) and a fusion gene with the 5'-flanking region of the angiotensinogen (ANG) gene linked to a bacterial chloramphenicol acetyl transferase (CAT) coding sequence as a reporter, pOCAT (ANG N-1498/ +18). Co-transfection of plasmid pBC-beta 1 AR or pBC-beta 2 AR alone enhanced the expression of pOCAT (ANG N-1498/+18). The addition of isoproterenol further stimulated the expression of pOCAT (ANG N-1498/ +18) when co-transfected with pBC-beta 1AR, but not with pBC-beta 2AR. Moreover, the addition of a combination of dexamethasone and isoproterenol synergistically stimulated the expression of pOCAT (ANG N-1498/+18) when co-transfected with pBC-beta 1AR, but not when cotransfected with pBC-beta 2AR. The synergistic effect of dexamethasone and isoproterenol was inhibited by the presence of RU 486 (an antagonist of glucocorticoid) or Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A I and II). To localize the putative cAMP-responsive element (CRE) and glucocorticoid responsive element (GRE) in the ANG gene, we constructed the fusion gene by inserting the DNA fragment, ANG N-806 to N-465 upstream of the thymidine kinase (TK) promoter fused to a CAT gene and introduced them with pBC-beta 1AR into OK cells. The addition of dexamethasone or isoproterenol alone stimulated the expression of pTKCAT (ANG N-806/-465). The addition of isoproterenol and dexamethasone synergistically stimulated the transcriptional activity of pTKCAT (N-806/-465). These studies demonstrate that the beta 1-adrenoceptor and dexamethasone act synergistically to stimulate the expression of the ANG gene in OK cells via the putative CRE and GREs in the 5'-flanking region of the rat ANG gene. These data should aid in the understanding of the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid induced expression of the ANG gene in the kidney.

Adrenergic beta-Agonists↗
PubMed1996

Dopaminergic receptors and angiotensinogen gene expression in opossum kidney cells.

To investigate whether expression of the renal angiotensinogen gene is regulated by dopaminergic receptors, we used opossum kidney (OK 27) cells with a fusion gene containing the 5'- flanking regulatory sequence of the rat angiotensinogen gene fused with a human growth hormone (hGH) gene as a reporter [pOGH, angiotensinogen nucleotide (N) -1498/+18], permanently integrated into their genomes. The level of expression of pOGH (angiotensinogen N-1498/+18) in OK 27 was evaluated by the amount of immunoreactive hGH (ir-hGH) secreted into the culture medium. In the absence of 3-isobutyl-1-methylxanthine (IBMX), addition of dopamine (10(-13) to 10(-5)M) had minimal effect on the expression of the pOGH (angiotensinogen N-1498/+18) in OK 27 cells. In the presence of IBMX, addition of low concentrations (10(-13) and 10(-7) M) of dopamine stimulated the expression of pOGH angiotensinogen N-1498/+18) in OK 27 cells in a dose-dependent manner, whereas high concentrations (i.e., > 10(-7) M) had minimal effect. The stimulatory effect of dopamine on the expression of pOGH (angiotensinogen N-1498/+18) was inhibited by the presence of SCH-23390 (D1-dopaminergic receptor antagonist) and spiperone (D2-dopaminergic receptor antagonist), but not by ketanserin (5 HT2/5HT1c-serotonergic receptor antagonist). Moreover, the stimulatory effect of dopamine was inhibited by the presence of U-73122 (an inhibitor of phospholipase C and phospholipase A2) or staurosporine (an inhibitor of protein kinase C) or (R)-p-adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMP[S]; an inhibitor of cAMP-dependent protein kinase AI and II). Addition of low concentrations (10(-13) to 10(-9)M) of SKF-82958 (D1-dopaminergic receptor agonist) or PPHT (D2-dopaminergic receptor agonist) also stimulated the expression of pOGH (angiotensinogen N-1498/+18). The stimulatory effect of SKF-82958 was inhibited by the presence of SCH-23390 or Rp-cAMP[S], whereas the effect of PPHT was inhibited by the presence of spiperone or staurosporine. These studies demonstrate that the expression of pOGH (angiotensinogen N-1498/+18) in OK 27 cells is modulated by dopaminergic receptor agonists.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Alpha-adrenoceptors and angiotensinogen gene expression in opossum kidney cells.

To investigate whether alpha (alpha)-adrenoceptor agonists have a stimulatory effect on the expression of the angiotensinogen (Ang) gene in opossum kidney (OK) cells, we used OK 27 cells with a fusion gene containing the 5'-flanking regulatory sequence of the rat angiotensinogen gene fused with a human growth hormone (hGH) gene as a reporter, pOGH (Ang N-1498/+18), permanently integrated into their genomes. The level of expression of the pOGH (Ang N-1498/+18) was quantitated by the amount of immunoreactive-human growth hormone (IR-hGH) secreted into the medium. The addition of iodoclonidine (alpha 2-adrenoceptor agonist, 10(-13) to 10(-9) M) and phorbol 12-myristate 13-acetate (PMA, 10(-13) to 10(-5) M) stimulated the expression of pOGH (Ang N-1498/+18) in a dose-dependent manner, whereas the addition of phenylephrine (alpha 1-adrenoceptor agonist, 10(-13) to 10(-5) M) had no effect. The stimulatory effect of iodoclonidine was blocked by the presence of yohimbine (alpha 2-adrenoceptor antagonist) and staurosporine (an inhibitor of protein kinase C) but not blocked by the presence of prazosin (alpha 1-adrenoceptor antagonist) or Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A). The addition of iodoclonidine, phenylephrine or PMA had no effect on the expression of pTKGH in OK 13 cells, an OK cell line, into which had been stably integrated a fusion gene, pTKGH containing the promoter/enhancer DNA sequence of the viral thymidine-kinase (TK) gene fused with a human growth hormone gene as a reporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1995

Expression of the angiotensinogen gene is synergistically stimulated by 8-BrcAMP and Dex in opossum kidney cells.

We transiently transfected fusion genes with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase (CAT) coding sequence as a reporter into opossum kidney (OK) cells. The addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) (10(-3)-10(-7) M) or forskolin (10(-9)-10(-5) M) stimulated the expression of the plasmid pOCAT [angiotensinogen nucleotide (N) -1498/+18] fusion gene in OK cells in a dose-dependent manner. The addition of dexamethasone (Dex) (10(-6) M) further enhanced the stimulatory effect of 8-BrcAMP or forskolin, whereas the addition of (R)-p-adenosine 3',5'-cyclic monophosphorothioate [(Rp)-cAMP[S], an inhibitor of cAMP-dependent protein kinase A, I and II] blocked the stimulatory effect of 8-BrcAMP. Furthermore, the addition of 8-BrcAMP (10(-3) M) or Dex (10(-6) M) or a combination of both stimulated the expression of pOCAT (angiotensinogen N -1138/+18), pOCAT (angiotensinogen N -960/+18), pOCAT (angiotensinogen N -814/+18), and pOCAT (angiotensinogen N -688/+18), but had no effect on the expression of pOCAT (angiotensinogen N -280/+18), pOCAT (angiotensinogen N -198/+18), pOCAT (angiotensinogen N -110/+18), pOCAT (angiotensinogen N -53/+18), and pOCAT (angiotensinogen N -35/+18). To further localize the putative cAMP-responsive element (CRE) in the angiotensinogen gene, we constructed fusion genes by inserting the DNA fragments angiotensinogen N -814 to N -689, angiotensinogen N -814 to N -761, and angiotensinogen N -760 to N -689 of the 5'-flanking region of the angiotensinogen gene upstream of the thymidine kinase (TK) promoter fused to a CAT gene and introduced them into OK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Beta-adrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro.

We have previously reported that addition of 8-bromocyclic AMP enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is known to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adrenergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10(-9) to 10(-5) mol/L) alone had no stimulatory effect on the expression of pOCAT (ANG N-1498/+18). In the presence of dexamethasone (10(-6) mol/L), however, isoproterenol enhanced the stimulatory effect on the dexamethasone on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta 1- and beta 2-adrenergic receptor antagonist) and ICI 118,551 (beta 2-adrenergic receptor antagonist) but not by the presence of atenolol (beta 1-adrenergic receptor antagonist). Furthermore, the addition of Rp-cAMP (an inhibitor of protein kinase A I and II) blocked the enhancing effect of isoproterenol. These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta 2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid-induced expression of the angiotensinogen gene in the liver.

Angiotensin II↗
PubMed1994

Isoproterenol and 8-bromo-cyclic adenosine monophosphate stimulate the expression of the angiotensinogen gene in opossum kidney cells.

To investigate whether the expression of the renal angiotensinogen (ANG) gene is regulated by beta-adrenoceptors and the cAMP-dependent protein kinase A pathway, we introduced stably the fusion gene containing the 5'-flanking regulatory sequence of the ANG gene with a human growth hormone (hGH) gene as a reporter, pOGH (ANG N-1498/+18), into opossum kidney (OK) cells. We successfully obtained several stable transformants with a high expression of the pOGH (ANG N-1498/+18) fusion gene. One stable transformant (OK 27) that is able to maintain the expression of pOGH (ANG N-1498/+18) in culture for more than a year was used in the present study. The level of expression of the pOGH (ANG N-1498/+18) in OK 27 was evaluated by the amount of immunoreactive-hGH (IR-hGH) secreted into the culture medium. The addition of isoproterenol (10(-11) M to 10(-9) M) stimulated the expression of pOGH (ANG N-1498/+18) and increased the accumulation of intracellular cAMP. Higher concentrations of isoproterenol (that is, greater than 10(-9) M) had low or minimal effect. In contrast, the addition of 8-bromo-cAMP (8-Br-cAMP) and forskolin stimulated the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner. The stimulatory effect of isoproterenol was blocked by the presence of propranolol, atenolol and ICI 118,551. The addition of ICI 118,551, however, was less effective than atenolol. Furthermore, the stimulatory effect of isoproterenol and 8-Br-cAMP on the expression of the pOGH (ANG N-1498/+18) was inhibited by the presence of Rp-cAMP (an inhibitor of cAMP-dependent protein kinase A I and II).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

ACMC: past, present and future.

In this article, the president of the Association of Canadian Medical Colleges (ACMC) and its director of research review the issues that have confronted ACMC since its inception: the founding of ACMC; development of the clinical teaching unit; creation of the Medical Research Council and expansion of the research mission; the Royal Commission on Health Services and the founding of new faculties of medicine; ACMC's in-house research program; accreditation and ACMC's links with medical education in the United States; and French-language medical education in Canada. The review points out the perennial nature of many of these issues, and how often perceived solutions to the problems later become problems themselves. It ends on the optimistic note that ACMC can successfully meet the challenges of the future.

Canada↗
PubMed1993

Hormonal regulation of expression of the angiotensinogen gene in cultured mouse hepatoma cells.

To investigate the hormonal regulation of expression of the angiotensinogen (ANG) gene in the liver, we constructed fusion genes with various lengths of the 5'-flanking region of the rat ANG gene linked to a bacterial chloramphenicol acetyl transferase (CAT) gene as reporter and introduced them into mouse hepatoma cells (Hepa 1-6). As a negative control, we introduced them into a nonhepatic cell line, a mouse testicular Sertoli (TM4) cell line. The level of expression of ANG-CAT fusion genes, pOCAT (ANG N-1498/+18), pOCAT (ANG N-688/+18), pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and (ANG-35/+18) were 3.7, 4, 1.1, 4, and 3-fold higher than promoterless pOCAT in Hepa 1-6 cells. No significant expression of any of these ANG-CAT fusion genes over the promoterless pOCAT was observed in Sertoli TM4 cells. The addition of dexamethasone (10(-10) to 10(-4) mol/L) stimulated the expression of the pOCAT (ANG N-1498/+18) fusion gene in Hepa 1-6 cells in a dose-dependent manner with a maximum stimulation at 10(-4) mol/L and a half-maximal stimulation at 10(-8) mol/L. A combination of dexamethasone (10(-6) mol/L) and 8-bromo-cyclic AMP (cAMP) (10(-3) mol/L) further enhanced the effect of the dexamethasone alone although cAMP alone had no effect. Testosterone (10(-6) mol/L), estradiol (10(-6) mol/L), progesterone (10(-6) mol/L), and thyroid hormone (L-T3, 10(-6) mol/L) did not have this effect in either the presence or absence of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1992

Hormonal regulation of expression of the angiotensinogen gene in cultured opossum kidney proximal tubular cells.

Angiotensinogen (ANG) messenger RNA is expressed in cultured opossum kidney (OK) proximal tubular cells. The aim of these studies was to investigate whether steroid hormones (dexamethasone, estradiol, testosterone, and progesterone) could stimulate the expression of renal ANG gene in vitro. Fusion genes consisting of various lengths of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase (CAT) reporter gene were constructed and introduced into cultured OK cells. The level of expression of fusion genes was determined by the level of cellular CAT enzymatic activity. The addition of dexamethasone (10(-12) to 10(-6) M) stimulates the expression of the pOCAT (ANG N-1498/+18) fusion gene in OK cells in a dose-dependent manner with a maximum stimulation at 10(-6) M and a half-maximal stimulation at 10(-9) M. Combination of dexamethasone (10(-6) M) and thyroid hormone, L-T3 (10(-6) M), further enhanced the effect of the dexamethasone alone. Testosterone (10(-6) M), estradiol (10(-6) M), and progesterone (10(-6) M) did not have this effect. Moreover, dexamethasone also stimulates the expression of the pOCAT (ANG N-688/+18) but not pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and pOCAT (ANG N-35/+18). These studies demonstrate that the glucocorticoid hormone is effective at stimulating the transcription of the ANG gene in OK cells, but stimulation is not observed from testosterone, estradiol, or progesterone. Moreover, glucocorticoid and L-T3 act synergistically to stimulate the transcription of the ANG gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1992

Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells.

Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0-, 12-, and 2.5-fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(-7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N-35/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1990

Molecular cloning and expression of the rat angiotensinogen gene.

To identify tissue- and hormonal-specific DNA control cis-elements in the rat gene, we have constructed fusion genes consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone (hGH) reporter gene and have introduced them into a subclone of rat pancreatic islet tumor cell line (1056A) which expresses the highest level of angiotensinogen mRNA. As a negative control, we have also introduced them into a human choriocarcinoma cell line (JEG-3), which does not express the endogenous angiotensinogen gene. The level of the expression of these fusion genes in these cells was determined by the level of immunoreactive hGH secreted into the culture medium. The expression of angiotensinogen-growth hormone (ANG-GH) fusion genes, pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 1.0, 1.8, 1.5, 12.0 and 3.0-fold higher, respectively, than the promoterless growth hormone expression vector (pOGH). The addition of dexamethasone (10(-6) M), aldosterone (10(-5) M), and thyroid hormone, L-T3 (10(-7) M), stimulated the expression of pOGH (ANG N-1498/+18) by 4.0-, 2.5-, and 2.0-fold above the control level, respectively. Combination of dexamethasone (10(-6) M), L-T3 (10(-7) M), and ethinyl-estradiol (10(-6) M) stimulated the expression of the pOGH (ANG N-1498/+18) to greater than 10-fold over the control. Ethinyl-estradiol (10(-6) M) or progesterone (10(-6) M) alone had no effect on the expression of the pOGH (ANG N-1498/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1990

Future prospects and strategies for academic medicine in Quebec.

Complete reorganization of the Quebec health and social services system, as envisaged by a new bill to be studied by the provincial government, is of major importance for the future of academic medicine since it includes all aspects of the training of health care professionals. While the bill aims to stimulate fundamental and applied research to the highest standards of academic medicine, its clearly stated spending limitations are a major concern to academic physicians. With the proposed centralization of all health care institutions, the role of medical schools and universities will be significantly diminished. Scientific programs of international standing and high levels of teaching and training of medical students and residents, on the other hand, can only be achieved with the development of appropriate structures. Effective prioritization, planning and representation of academic institutions must therefore be given as much consideration as the equally important functions of health care, teaching, and research. Programs oriented toward personnel support and the development of research centres and institutes should continue to be fostered. The future of academic medicine, particularly in its clinical components, is closely linked to the health care system. Academic physicians must become involved in the strategic planning of health care delivery since the development of academic medicine will otherwise not flourish.

Academic Medical Centers↗
PubMed1989

The kidney in essential hypertension: culprit or victim?

Clinical and experimental data clearly demonstrate that, at least in some forms of hypertension, removal of the kidney and its replacement by a non-hypertensinogenic organ may counteract the development of this disease. Although their specific involvement has yet to be determined, a number of vasoactive and sodium-retaining systems originating from the kidney are important in blood pressure control and play a key role in essential hypertension. Even if the triggering mechanisms do not lie within this organ, the kidney is at least an essential link for the expression of essential hypertension.

Humans↗
PubMed1987

Catecholamine sulfates: end products or metabolic intermediates?

Dopamine-beta-hydroxylase catalyzes the beta-oxidation of dopamine to noradrenaline while phenylethanolamine-N-methyltransferase converts noradrenaline to adrenaline. Since catecholamine sulfates represent the predominant form of catecholamines in human tissues, we have studied the role of dopamine sulfate and noradrenaline sulfate as alternate substrates for dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, respectively. Dopamine 3-sulfate, dopamine 4-sulfate and noradrenaline 3-sulfate were chemically synthesized and exhaustively purified by ion-exchange chromatography. Dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase were partially purified from human adrenals. Using tyramine as substrate, dopamine-beta-hydroxylase is slightly inhibited by dopamine 3-sulfate according to some irreversible or mixed mechanisms. When dopamine-beta-hydroxylase was incubated with dopamine 3-sulfate or dopamine 4-sulfate, we were not able to find any synthesis of either noradrenaline sulfate or free noradrenaline. Using phenylethanolamine as substrate, the enzymatic activity of phenylethanolamine-N-methyltransferase remains unchanged with addition of dopamine 3-sulfate, dopamine 4-sulfate or noradrenaline 3-sulfate. It was concluded that dopamine sulfate is not an alternate substrate for either dopamine-beta-hydroxylase or phenylethanolamine-N-methyltransferase nor is noradrenaline 3-sulfate an alternate substrate for phenylethanolamine-N-methyltransferase.

Adult↗