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J T Turner

Publications and source records attributed to J T Turner.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy.

The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be bypassed by an alternative pathway for Cl- transport that is activated by extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect is a therapeutic target for improving Cl- secretion in CF patients. In this paper, we report the sequence and functional expression of a cDNA cloned from human airway epithelial (CF/T43) cells that encodes a protein with properties of a P2U nucleotide receptor. With a retrovirus system, the human airway clone was stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to extracellular nucleotides. Studies of inositol phosphate accumulation and intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 cells expressing the receptor identified this clone as the target receptor in human airway epithelia. In addition, we independently isolated an identical cDNA from human colonic epithelial (HT-29) cells, indicating that this is the same P2U receptor that has been functionally identified in other human tissues. Expression of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 1321N1 cell line will be useful for studying autocrine regulatory mechanisms and in screening of potential therapeutic drugs.

Adenosine Triphosphate↗
PubMed1994

Integrative Cloning, Expression, and Stability of the cryIA(c) Gene from Bacillus thuringiensis subsp. kurstaki in a Recombinant Strain of Clavibacter xyli subsp. cynodontis.

A bacterial endophyte was engineered for insecticidal activity against the European corn borer. The cryIA(c) gene from Bacillus thuringiensis subsp. kurstaki was introduced into the chromosome of Clavibacter xyli subsp. cynodontis by using an integrative plasmid vector. The integration vectors pCG740 and pCG741 included the replicon pGEM5Zf(+), which is maintained in Escherichia coli but not in C. xyli subsp. cynodontis; tetM as a marker for selection in C. xyli subsp. cynodontis; and a chromosomal fragment of C. xyli subsp. cynodontis to allow for homologous recombination between the vector and the bacterial chromosome. Insertion of vector DNA into the chromosome was demonstrated by DNA hybridization. Recombinant strains MDR1.583 and MDR1.586 containing the cryIA(c) gene were shown to produce the 133,000-kDa protoxin and several smaller immunoreactive proteins. Both strains were equally toxic to insect larvae in bioassays. Significant insecticidal activity was demonstrated in planta. The cryIA(c) gene and the tetM gene introduced into strain MDR1.586 were shown to be deleted from some cells, thereby giving rise to a noninsecticidal segregant population. In DNA hybridization experiments and insect bioassays, these segregants were indistinguishable from the wild-type strain. Overall, these results demonstrate the plausibility of genetically engineered bacterial endophytes for insect control.

Journal Article↗
PubMed1994

D2 dopamine receptor response to endophyte-infected tall fescue and an antagonist in the rat.

Effects on rat brain D2 dopamine receptors by endophyte-infected tall fescue seed consumption and antagonist injection were characterized. Forty-eight male Wistar rats (225 g) in three separate trials were exposed to either 22 or 32 degrees C. Diets, to maintain similar concentrations of ergovaline, contained 10% (Trial 1) or 15% (Trials 2 and 3) endophyte-infected (E+; 325 average ppb of ergovaline) or uninfected (E-; 0 ppb of ergovaline) tall fescue seed. Rats were injected i.p. daily with either placebo (PL) or an experimental D2 dopamine antagonist (DA, .0375 mg/kg BW). No effects (P > .10) on diet DM intake by E+ ingestion or DA injection were detected at 22 degrees C. However, ingestion of E+ reduced (P < .01) and injection of DA improved (P < .05) DM intake of rats housed in 32 degrees C (11.1 vs 15.4 g of DM/d for E+ vs E-, respectively). Whole brain D2 dopamine receptor density (Bmax) and mRNA were reduced (P < .05) by E+ and increased (P < .05) by DA in Trial 1. No treatment effects (P > .10) on cerebral cortex alpha 1- and alpha 2-adrenergic or striatal D2 dopamine receptor Bmax were measured in Trials 2 and 3. In summary, dietary E+ reduced whole brain D2 dopamine mRNA and Bmax, whereas injection of DA increased D2 dopamine mRNA. Thus, long-term regulation of monoamine receptors seems to be affected by E+ ingestion or DA injection.

Animals↗
PubMed1993

Functional expression and photoaffinity labeling of a cloned P2U purinergic receptor.

ATP and UTP can function as extracellular signaling molecules by activating plasma membrane receptors termed P2 purinergic receptors. In the present study a P2U receptor cDNA has been expressed in K-562 human leukemia cells, one of the few available mammalian cell lines that lacks an endogenous P2U receptor. In stably transfected cells, low micromolar concentrations of ATP or UTP activated the receptor, resulting in the mobilization of intracellular calcium but not the influx of extracellular calcium. A photoaffinity agonist of the P2U receptor, 3'-O-(4-benzoylbenzoyl)adenosine 5'-[alpha-32P]triphosphate ([alpha-32P]BzATP), photolabeled several proteins in plasma membranes from the stable transfectant or from untransfected K-562 cells. The photolabeling of a 53-kDa protein was significantly greater in plasma membranes from the stable transfectant than from untransfected cells. A mutant receptor containing six consecutive histidine residues at its carboxyl terminus was constructed and used to verify that this 53-kDa protein was the P2U receptor. In plasma membranes from cells expressing the histidine-tagged P2U receptor, but not from cells expressing the wild-type receptor, a single [alpha-32P]BzATP-labeled protein with a molecular mass of 53 kDa was retained on a Ni(2+)-charged Sepharose column, which binds many proteins containing a polyhistidine tag. Photolabeling of the 53-kDa protein by [alpha-32P]BzATP was inhibited by ATP but not by UTP, raising the possibility that the P2U receptor may have distinct binding sites for each nucleotide.

Adenosine Triphosphate↗
PubMed1993

Recidivism and mental illness: the role of communities.

This study examined the impact of community characteristics on rehospitalization of chronically mentally ill (CMI) clients from public psychiatric hospitals in Virginia. The relationship between rehospitalization, often termed recidivism, and community attributes was explained within the theoretical context of community ecology (Hawley 1950). A small area analysis approach that employed path analysis was used to assess the relationship between rehospitalization and selected community variables including: available health care resources, socioeconomic factors, race, presence of psychopathology, and household composition. The path model was estimated and validated using a linear structural relations computer program (LISREL VI). Results reveal female-headed households and socioeconomic status to be significant predictors of rehospitalization. A discussion of implications of the findings for community mental health services delivery and research is provided.

Chronic Disease↗
PubMed1993

Guanylin stimulation of Cl- secretion in human intestinal T84 cells via cyclic guanosine monophosphate.

Intestinal salt and fluid secretion is stimulated by Escherichia coli heat-stable enterotoxins (ST) through activation of a membrane guanylate cyclase found in the intestine. Guanylin is an endogenous intestinal peptide that has structural similarity to the bacterial peptides. Synthetic preparations of guanylin or E. coli ST 5-17 stimulated Cl- secretion in T84 cells cultured on semipermeable membranes as measured by increases in short circuit current (Isc). The guanylin/ST receptors appeared to be on the apical surface of T84 cells, since addition of guanylin to the apical, but not basolateral, reservoir stimulated Isc. Bumetanide added to the basolateral side effectively inhibited the Isc responses of T84 cells to either guanylin or ST 5-17. Guanylin appeared to be about one-tenth as potent as ST in stimulating transepithelial Cl- secretion. Guanylin and E. coli ST 5-17 both caused massive (> 1,000-fold) increases in cGMP levels in T84 cells, but guanylin was less potent than ST. Both peptides fully inhibited the binding of 125I-ST to receptor sites on intact T84 cells. The radioligand binding data obtained with guanylin or ST 5-17 best fit a model predicting two receptors with different affinity for these ligands. The Ki values for guanylin were 19 +/- 5 nM and 1.3 +/- 0.5 microM, whereas the Ki values for ST 5-17 were 78 +/- 38 pM and 4.9 +/- 1.4 nM. We conclude that guanylin stimulated Cl- secretion via the second messenger, cGMP, in T84 human colon cells. At least two guanylin receptors with different affinities for these ligands may exist in the cultured T84 cells. It may be postulated that guanylin is an endogenous hormone that controls intestinal Cl- secretion by a paracrine mechanism via cGMP and that E. coli ST stimulates Cl- secretion by virtue of an opportunistic mechanism through activation of guanylin receptors.

Bacterial Toxins↗
PubMed1992

Regulation of secretion by vasoactive intestinal peptide in isolated perfused rat submandibular glands.

The isolated, perfused gland was used to examine the regulation of saliva volume and protein content by vasoactive intestinal peptide (VIP). In the absence of other secretagogues, VIP produced a modest, sustained saliva flow with a biphasic dose-response curve in which saliva volume was greatest at 1 nM VIP (28.5 +/- 3.8 microliters in the first 5 min, n = 4) but reduced at lower and higher concentrations. The protein concentration in saliva released in response to VIP (0.86 +/- 0.13 micrograms/microliters) was substantially higher than with 30 nM acetylcholine (0.06 +/- 0.02 micrograms/microliters) or 1 nM substance P (0.30 +/- 0.05 micrograms/microliters). During the first 5 min of stimulation, VIP and substance P were synergistic in terms of volume and protein content whereas inclusion of VIP did not increase acetylcholine-stimulated flow in the first 5 min but produced a higher sustained flow over the next hour. After stimulation with acetylcholine, subsequent addition of VIP transiently enhanced saliva volume and protein content in a monophasic, dose-dependent manner with effects at 1 pM VIP and higher. The responses were different for VIP compared with other cAMP-mobilizing agents and the involvement of multiple VIP receptor subtypes was suggested from experiments in which a VIP antagonist blocked the VIP enhancement of saliva volume but not the increase in protein.

Acetylcholine↗
PubMed1992

Potentiation of cyclic adenosine monophosphate production by thrombin in the human erythroleukemia cell line, HEL.

The human erythroleukemia cell line (HEL) has been used as a model system for studying signal transduction processes as they might relate to platelet/megakaryocyte function. We were interested in examining the role of thrombin in the regulation of adenylyl cyclase in this cell line. As opposed to its predominantly inhibitory effects on cyclic AMP production in platelets or in membranes from HEL cells, our initial experiments in intact HEL cells revealed that thrombin markedly potentiated the cyclic AMP response to prostaglandin E1 (2.9 +/- 0.2-fold), prostacyclin (1.9 +/- 0.2-fold) and carbacyclin (2.5 +/- 0.5-fold), measured either by radioimmunoassay or by the [3H]adenine preloading procedure. Thrombin, although ineffective alone, also potentiated cyclic AMP production stimulated by vasoactive intestinal peptide (1.6 +/- 0.2-fold), cholera toxin (3.0 +/- 0.6-fold) and AIF4- (2.3 +/- 0.6-fold), but not by forskolin (0.9 +/- 0.1-fold). The thrombin effect 1) produced an increase in the efficacy of the prostaglandins with no change in potency; 2) was long-lived; 3) required the proteolytic activity of thrombin; 4) was insensitive to pertussis toxin; and 5) was at least partially mimicked by trypsin, extracellular ATP and UTP, platelet activating factor and activators of protein kinase C. Down-regulation of protein kinase C or pre-exposure to the protein kinase inhibitor staurosporine blocked the potentiating effect. Together, these results suggest that in HEL cells, the mechanism of thrombin potentiation of cyclic AMP production may involve alterations in the interaction between stimulatory guanine nucleotide binding protein and the catalytic subunit of adenylyl cyclase, possibly involving protein kinase C-mediated phosphorylation.

Adenylyl Cyclases↗
PubMed1991

Identification of functional receptors for vasoactive intestinal peptide and neurotensin in the human submandibular gland duct cell line, HSG-PA.

The HSG-PA human submandibular gland adenocarcinoma cell line has attracted attention recently as a potentially useful cell culture model for studies of salivary duct cell function and regulation. These cells possess a variety of morphological and biochemical markers found in salivary duct cells. Recently, muscarinic cholinergic receptors coupled to inositol intracellular Ca2+ mobilization (He et al., Eur. J. Physiol., 413 (1989) 505-510) and K+ fluxes (Ship et al., Am. J. Physiol., 259 (1990) C340-C348) have been identified in HSG-PA cells. In this study, we report the presence in these cells of functional receptors for two neuropeptides, vasoactive intestinal peptide (VIP) and neurotensin. Receptors for both peptides were labeled in intact cell radioligand binding studies and exhibited pharmacological profiles similar to receptors found in other tissues. There was close agreement between binding Ki values and the ED50 values for stimulation of second messenger production and modulation of K+ efflux, with all values between 1 and 5 nM. Whereas neurotensin stimulated K+ efflux dramatically, VIP alone had no effect but enhanced the response to neurotensin. These studies thus represent the initial documentation of functional receptors for VIP and neurotensin in a cell line of salivary duct cell origin.

Adenocarcinoma↗
PubMed1991

Stability of the delta-endotoxin gene from Bacillus thuringiensis subsp. kurstaki in a recombinant strain of Clavibacter xyli subsp. cynodontis.

Deletion of chromosomally inserted gene sequences from Clavibacter xyli subsp. cynodontis, a xylem-inhabiting endophyte, was studied in vitro and in planta. We found that nonreplicating plasmid pCG610, which conferred resistance to kanamycin and tetracycline and contained segments of C. xyli subsp. cynodontis genomic DNA, integrated into a homologous sequence in the bacterial chromosome. In addition, pCG610 contains two copies of the gene encoding the CryIA(c) insecticidal protein of Bacillus thuringiensis subsp. kurstaki HD73. Using drug resistance phenotypes and specific DNA probes, we found that the loss of all three genes arose both in vitro under nonselective conditions and in planta. The resulting segregants are probably formed by recombination between the repeated DNA sequences flanking pCG610 that resulted from the integration event into the chromosome. Eventually, segregants predominated in the bacterial population. The loss of the integrated plasmid from C. xyli subsp. cynodontis revealed a possible approach for decreasing the environmental consequences of recombinant bacteria for agricultural use.

Bacillus thuringiensis↗
PubMed1991

Regulation of calcium-activated potassium efflux by neurotensin and other agents in HT-29 cells.

Neurotensin receptors have been shown previously to be coupled to polyphosphoinositide turnover and intracellular Ca2+ ([Ca2+]i) mobilization in HT-29 colonic epithelial cells (Bozou et al. Biochem. J. 264: 871, 1989; Turner et al. J. Pharmacol. Exp. Ther. 253: 1049, 1990). In this study, neurotensin was found to enhance dramatically the Ba2(+)- and tetraethylammonium chloride-sensitive K(+)-efflux rate (measured with 86Rb+) in the presence of ouabain and bumetanide, with basal efflux increasing 4.5 +/- 0.5-fold with 10 nM neurotensin. The K(+)-efflux rate, which was partially dependent on the extracellular Ca2+ concentration, was also increased by carbachol and ATP, two other [Ca2+]i-mobilizing agonists in HT-29 cells, as well as by the Ca2+ ionophores ionomycin and A23187, suggesting that the efflux was through Ca2(+)-activated K+ channels. Pretreatment of cells with neurotensin, carbachol, or ATP desensitized subsequent neurotensin-stimulated efflux by 82, 57, and 63%, respectively, confirming our previous results which indicated homologous and heterologous desensitization of the neurotensin receptor-signal transduction pathway. Pretreatment of cells with the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and mezerein did not affect [Ca2+]i mobilization or K+ efflux directly but desensitized neurotensin-stimulated efflux by greater than 80%. Pretreatment (2 h) with PMA also decreased K+ efflux in response to ionomycin by 59%, although ionomycin-induced [Ca2+]i mobilization was not inhibited. Downregulation of protein kinase C by overnight pretreatment with PMA resulted in recovery of ionomycin-stimulated efflux. These results suggest that agonist-stimulated Ca2(+)-activated K+ channels in HT-29 cells are regulated at multiple steps in the signal transduction pathway.

Adenocarcinoma↗
PubMed1991

Activation of phospholipase D by E-series prostaglandins in human erythroleukemia cells.

Phospholipase D (PLD) can be activated by a variety of receptor agonists in different cell types. However, an effect of prostaglandins (PGs) on the activity of this enzyme has not been demonstrated previously. In this study, we found that PGE1 could stimulate PLD in human erythroleukemia cells, as measured by phosphatidylethanol formation, with an ED50 of 3.5 x 10(-7) M. PGE2 was also active, but other PGs including prostacyclin, PGD2 and PGF2, had no effect. PGE1 also elicited cyclic AMP production over the same concentration range that activated PLD. However, it is unlikely that cyclic AMP per se is responsible for PGE-induced PLD activation, because PLD could be substantially activated by PGE2 at concentrations (0.1-1 microM) which did not stimulate cyclic AMP production. Furthermore, no increase of phosphatidylethanol formation could be observed when cells were treated with other adenylyl cyclase-activating agents such as prostacyclin, forskolin and vasoactive intestinal peptide. In Ca+(+)-free medium, PLD activation by PGE1 and PGE2 was greatly reduced, indicating that their effect was through a Ca+(+)-dependent pathway. Pretreatment of cells with pertussis toxin abolished PGE1- and PGE2-stimulated PLD activity, implying the involvement of a G protein in the PGE-mediated signal transduction pathway. Our results not only indicate that E-series PGs may initiate some of their cellular effects through a novel pathway, activation of PLD, but also suggest that PGE-stimulated PLD activity in human erythroleukemia cells is Ca+(+)-dependent and is regulated via a pertussis toxin-sensitive G protein.

Calcium↗
PubMed1991

Functional studies in the human submandibular duct cell line, HSG-PA, suggest a second salivary gland receptor subtype for nucleotides.

Extracellular nucleotides, acting through P2 purinoceptors, have been implicated in the regulation of ion transporting epithelia, including salivary gland acini. Multiple P2 purinoceptor subtypes have been suggested, including P2X, P2Y and P2U (or nucleotide) subtypes, as well as the P2Z subtype found in rat parotid acinar cells. We investigated responses to ATP, ATP analogs and UTP in transformed human submandibular gland duct cells (HSG-PA), in order to compare duct cell purinoreceptors with those in acinar cells. ATP, UTP and some ATP analogs increased, with different potencies, inositol phosphate accumulation, calcium mobilization and potassium efflux. Nucleotide-stimulated calcium mobilization occurred in the absence of, but was enhanced by, extracellular calcium, and maximal potassium efflux required extracellular calcium. UTP and ATP demonstrated equal potencies of about 1 microM and similar efficacies in eliciting these responses, and identical rank orders of potency for stimulating calcium mobilization and potassium efflux were obtained: UTP = ATP greater than ATP gamma S greater than ADP greater than ADP beta S, with alpha,beta-methylene-ATP and 2-methylthio-ATP having little or no effect. Agents reported to block nucleotide effects in parotid acini were ineffective in HSG-PA cells, and experiments in Mg(++)- and Ca(++)-free medium did not indicate that a form of ATP other than MgATP was the active species at the HSG-PA purinoceptor. The extracellular nucleotide effects were not altered by pertussis toxin. These results indicate the presence of a P2U or nucleotide receptor subtype in HSG-PA submandibular duct cells distinguishable from the P2Z purinoceptor of rat parotid acinar cells, suggesting involvement of multiple nucleotide receptor subtypes in salivary gland regulation.

Adenosine Triphosphate↗
PubMed1991

Measuring adolescent satisfaction with nursing care in an ambulatory setting.

This descriptive study addresses the topic of patient satisfaction with nursing care. A convenience sample of adolescent females who attended health department family planning clinics in a southeastern city was surveyed to determine the level of satisfaction with care provided by clinic nurses. Data were collected using the Risser Patient Satisfaction with Nursing Care instrument (Risser, 1975) which had been used exclusively with adults. A primary purpose, therefore, was to test the instrument with a teenage population. Data analysis yielded descriptive statistics, frequency distributions, correlations and alpha reliability coefficients. Findings indicated that the teenagers were most satisfied with the technical-professional aspect of nursing care and least satisfied with the interpersonal-educational aspect. The Risser instrument was found to be highly reliable with this adolescent cohort.

Ambulatory Care↗
PubMed1990

The influence of vasoactive intestinal peptide receptors in dispersed acini from rat submandibular gland on cyclic AMP production and mucin release.

Vasoactive intestinal peptide has been identified as an important regulator of submandibular salivary gland function, consistent with its localization with acetylcholine in parasympathetic neurones innervating this gland. Enzymatically dispersed acini from rat submandibular gland are a useful system in which to study gland regulation at the cellular level. Here, three aspects of vasoactive intestinal peptide interactions with acini were examined: inhibition of binding of [125I]-vasoactive intestinal peptide, stimulation of cyclic AMP production and enhancement of mucin release. Vasoactive intestinal peptide and peptide histidineisoleucineamide inhibited [125I]-vasoactive intestinal peptide binding to intact acini, with IC50 values of 16 +/- 3 and 46 +/- 17 nM, respectively. This rank order of potency agrees with that observed previously in assays using rat submandibular gland membranes and is similar to values obtained in assays measuring increases in cyclic AMP production in which the ED50 values for vasoactive intestinal peptide and peptide histidineisoleucineamide were 3.1 +/- 1.8 and 29 +/- 13 nM, respectively. Although vasoactive intestinal peptide stimulation of cyclic AMP production was only about 10% of that seen in response to isoproterenol, the levels of mucin release induced by the two agents were more similar. The ED50 for vasoactive intestinal peptide-stimulated mucin release was 0.12 +/- 0.05 nM, thus suggesting an activation anomaly in the vasoactive intestinal peptide receptor-coupled signal transduction pathway at a point between cyclic AMP production and mucin release.

Animals↗
PubMed1990

Characterization of the muscarinic cholinergic receptor in the opossum (Didelphis virginiana, Kerr) submandibular gland: differences in receptor density and subtype compared with higher mammalian species.

1. Kinetic, saturation and inhibition radioligand binding experiments with [3H]-N-methylscopolamine and [3H]quinuclidinyl benzilate were used to characterize the muscarinic cholinergic receptor in opossum (Didelphis virginiana, Kerr) submandibular salivary gland membranes. 2. The receptor density in opossum submandibular gland was found to be more than 3-fold higher than in rat, and 22-fold higher than in human, submandibular glands. 3. Inhibitor equilibrium dissociation constants for the antagonists pirenzepine, dicyclomine, atropine, N-methylscopolamine and AF-DX 116 revealed that the muscarinic receptor present in opossum submandibular gland appears to be the M1 subtype rather than the M3 subtype found in human and rat.

Animals↗
PubMed1990

Vasoactive intestinal peptide stimulates active K+ transport and Na(+)-K(+)-Cl- cotransport in HT-29 cells.

Regulation of active K+ influx and Na(+)-K(+)-Cl- cotransport activity in HT-29 cells by vasoactive intestinal peptide (VIP) was investigated. Both active K+ influx, defined as the ouabain-sensitive component, and Na(+)-K(+)-Cl- cotransport, defined as the ouabain-resistant bumetanide-sensitive component, of total K+ uptake were increased by VIP. VIP increased the maximum velocity (Vmax) values for both components with no change in apparent Michaelis constant (Km) values. Three lines of evidence support the role of adenosine 3',5'-cyclic monophosphate (cAMP) as a mediator of the VIP effects. 1) The rank order potencies of VIP and peptide histidineisoleucineamide (PHI) in binding and cAMP production (J. T. Turner, S. B. Jones, and D. B. Bylund, Peptides Fayetteville 7: 849, 1986) and K+ uptake were consistent; 2) alpha 2-adrenergic agonists inhibited both VIP-stimulated cAMP production (J. T. Turner, C. Ray-Prenger, and D. B. Bylund, Mol. Pharmacol. 28: 422, 1985) and K+ uptake; and 3) forskolin, but not dideoxyforskolin, mimicked the effects of VIP on K+ uptake. Because amiloride blocked the VIP-stimulated active K+ component, the VIP effects on active K+ influx may be secondary to a Na(+)-H+ antiporter-mediated increase in cellular Na+ content. Additional experiments indicated that pretreatment of cells with a protein kinase C activator, previously shown to decrease basal Na(+)-K(+)-Cl- cotransport activity and the apparent number of cotransporters in HT-29 cells (C. C. Franklin, J. T. Turner, and H. D. Kim, J. Biol. Chem. 264: 6667, 1989), did not change the magnitude of response of the remaining cotransporters after adenylate cyclase activation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗