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H M Cox

Publications and source records attributed to H M Cox.

At least 19 recordsLinked to original sources
PubMed2001

Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil factor) in the jejunum of transgenic mice.

To further examine the function of the trefoil factor family (TFF), the expression of which is up-regulated at sites of injury, we have produced transgenic mice that chronically express rat TFF3 within the jejunum (using a rat fatty acid-binding protein promoter). The expression of rat TFF3 was limited to the villi of the jejunum and had no effect on base-line morphology. Rat TFF3 expression did result, however, in a reduced sensitivity to indomethacin (85 mg/kg subcutaneously), which only caused a 29% reduction in villus height in transgenics versus 51% reduction in controls (p < 0.01). Indomethacin increased initial intestinal epithelial cell proliferation and migration, but the presence of rat TFF3 caused no additional change in proliferation (bromodeoxyuridine), cell migration ([(3)H]thymidine and bromodeoxyuridine), apoptosis (terminal deoxyuridine nucleotidyl nick end labeling), or E-cadherin immunostaining. In vitro studies following changes in resistance of intestinal strips in Ussing chambers (voltage-clamp technique) showed increased base-line resistance in the rat TFF3-expressing region (326 +/- 60 versus 195 +/- 48 ohm.cm(2) in controls, p < 0.05) and reduced the fall in resistance following HCl exposure by about 40% (p < 0.01). Overexpression of TFF3 stabilizes the mucosa against noxious agents, supporting its role in mucosal protection/repair. It may therefore provide a novel approach to the prevention and/or treatment of intestinal ulceration.

Animals↗
PubMed2001

Tachykinin NK(2) receptor mediates contraction and ion transport in rat colon by different mechanisms.

We have characterized the tachykinin NK(2) receptor-mediated contraction and vectorial ion transport responses in the muscularis mucosae and mucosa of the rat isolated distal colon, respectively. The tachykinin NK(2) receptor-selective antagonist nepadutant (c([(beta-D-GlcNAc)Asn-Asp-Trp-Phe-Dpr-Leu]c(2beta-5beta))) produced competitive antagonism of [betaAla(8)]neurokinin A-(4-10)-induced contraction (pK(B) = 9.3) in the muscularis mucosae, and insurmountable blockade of increases in short-circuit current (I(sc)) responses (pK(B) = 8.6) in the mucosa. However, this latter effect was completely reversed by washout of the antagonist. [betaAla(8)]Neurokinin A-(4-10)-induced contractions were unaffected by indomethacin (3 microM). In sharp contrast, I(sc) responses induced by [betaAla(8)]neurokinin A-(4-10) (100 nM) were inhibited (>70%) by indomethacin (3 microM), while I(sc) responses to substance P (3 microM) were unchanged. Our study provides the first evidence that in the same organ stimulation of tachykinin NK(2) receptors leads to two independent responses mediated by different effector mechanisms both of which are blocked (albeit with different kinetics) by the potent and selective tachykinin NK(2) receptor antagonist, nepadutant.

Animals↗
PubMed2001

Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa.

A functional study has been performed to characterise the Y receptors responsible for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations. Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln(23)hPP and rPP were effective but less potent than full length PYY, NPY or their Pro(34)-substituted analogues, while the Y(5) agonist Ala(31), Aib(32)hNPY was the least active peptide tested. The Y(1) antagonists, BIBP3226 and BIBO3304 virtually abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively inhibited by the Y(2) antagonist, BIIE0246. A combination of BIBO3304 and BIIE0246 also partially attenuated hPP responses, leaving residual effects that were most probably Y(4)-mediated. Thus we conclude that Y(1), Y(2) and Y(4) receptors attenuate ion secretion in mouse colon.

Animals↗
PubMed2001

Constitutive neuropeptide Y Y(4) receptor expression in human colonic adenocarcinoma cell lines.

1. Three human adenocarcinoma cell lines, Colony-24 (Col-24), Col-6 and Col-1 have been studied as confluent epithelial layers able to transport ions vectorially in response to basolateral vasoactive intestinal polypeptide (VIP) and pancreatic polypeptides (PP). 2. Different species PP stimulated responses in Col-24 with Y(4)-like pharmacology. Bovine (b)PP, human (h)PP and porcine (p)PP were equipotent (EC(50) values 3.0--5.0 nM) while rat (r)PP, avian (a)PP and [Leu(31), Pro(34)]PYY (Pro(34)PYY) were significantly less potent. PYY was inactive. The PP pharmacology in Col-1 was comparable with Col-24. However, Col-6 cells were different; pPP had an EC(50) intermediate (22.0 nM) between that of bPP (3.0 nM) and hPP (173.2 nM), with aPP and rPP being at least a further fold less potent. 3. Deamidation of Tyr(36) in bPP (by O-methylation or hydroxylation) or removal of the residue resulted in significant loss of activity in Col-24. 4. GR231118 (1 microM) had no PP-like effects. In Col-24 and Col-1, GR231118 significantly attenuated bPP (30 nM) or hPP (100 nM) responses, but it did not alter bPP responses in Col-6. BIBP3226 and GR231118 both inhibited Y(1)-mediated responses which were only present in Col-6. 5. RT--PCR analysis confirmed the presence of hY(4) receptor mRNA in Col-24 and Col-1 epithelia but a barely visible hY(4) product was observed in Col-6 and we suggest that an atypical Y(4) receptor is expressed in this cell line.

Adenocarcinoma↗
PubMed2000

PYY preference is a common characteristic of neuropeptide Y receptors expressed in human, rat, and mouse gastrointestinal epithelia.

This investigation describes the relative potencies of four peptide agonists, namely, peptide YY (PYY), [Leu3l,Pro34]PYY (Pro34pYY), neuropeptide Y (NPY), and [Leu31,Pro34]NPY (Pro34NPY), as antisecretory agents in human, rat, and mouse gastrointestinal preparations. The inhibition of agonist responses by the Y1-receptor antagonist BIBP 3226 was also tested in each preparation. An unexpectedly pronounced preference for PYY and Pro34PYY was observed in functional studies of two human epithelial lines stably transfected with the rat Y1 receptor (Y1-7 and C1Y1-6). NPY and Pro34NPY were at least an order of magnitude less effective than PYY in these functional studies but were only marginally less potent in displacement binding studies using membrane preparations of the same clonal lines. The orders of agonist potency obtained in Y1-7 and C1Y1-6 epithelia were compared with those obtained from a single human colonic adenocarcinoma cell line (Colony-6, which constitutively expresses Y1 receptors) and also from mucosal preparations of rat and mouse descending colon. Similar peptide orders of potency were obtained in rat and mouse colonic mucosae and Colony-6 epithelia, all of which exhibited PYY preference (although less pronounced than with Y1-7 and C1Y1-6 epithelia) and significant sensitivity to the Y1 receptor antagonist, BIBP 3226. We have compared the pharmacology of these five mammalian epithelial preparations and provide cautionary evidence against the reliance upon agonist concentration-response relationships alone, in the characterization of NPY receptor types.

Animals↗
PubMed1999

Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line.

1. Short-circuit current (I(SC)) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA-7 adenocarcinoma cell line. In Krebs-Henseleit (KH) buffer, CCh responses consisted of three I(SC) components: an unusual rapid decrease (the 10 s spike) followed by an upward spike at 30 s and a slower transient increase (the 2 min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP-stimulated I(SC). 2. In HCO3- free buffer, the decrease in forskolin-elevated I(SC) after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl- anions were replaced by gluconate, both Ca2+- and cyclic AMP-mediated electrogenic responses were significantly inhibited. 3. Basolateral Ba2+ (1-10 mM) and 293B (10 microM) selectively inhibited forskolin stimulation of I(SC), without altering the effects of CCh. Under Ba2+- or 293B-treated conditions, CCh responses were potentiated by pretreatment with forskolin. 4. Basolateral charybdotoxin (50 nM) significantly increased the size of the 10 s spike of CCh responses in both KH and HCO3- free medium, without affecting the 2 min peak. The enhanced 10 s spike was inhibited by prior addition of 5 mM apical Ba2+. Charybdotoxin did not affect forskolin responses. 5. In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, both at 100 nM) abolished subsequent 10 microM CCh responses. Following addition of p-fluoro hexahydro-sila-difenidol (pF-HHSiD, 10 microM) or pirenzepine (1 microM), qualitative changes in the CCh response time-profile also indicated a rightward shift of the agonist concentration-response curve; however, 1 microM gallamine had no effect. These results suggest that a single M3-like receptor subtype mediates the secretory response to CCh. 6. It is concluded that CCh and forskolin activate discrete populations of basolateral K+ channels gated by either Ca2+ or cyclic AMP, but that the Cl- permeability of the apical membrane may limit their combined effects on electrogenic Cl- secretion. In addition, CCh activates a Ba2+-sensitive apical K+ conductance leading to electrogenic K+ transport. Both agents may also modulate HCO3- secretion through a mechanism at least partially dependent on carbonic anhydrase.

Acetazolamide↗
PubMed1998

Structure-activity relationships with neuropeptide Y analogues: a comparison of human Y1-, Y2- and rat Y2-like systems.

A structure-activity study utilising 36 synthetic Ala-analogues of the 36-residue oligopeptide neuropeptide Y (NPY) has been performed with mucosal preparations from the rat jejunum (Y2-like receptor) and compared with receptor displacement binding in the human neuroblastoma cell lines, SMS-KAN, (Y2-receptors) and SK-N-MC cells (Y1-receptors). Each amino acid of the natural sequence was replaced by L-alanine, and the four intrinsic alanine residues at position 12, 14, 18 and 23 were replaced by glycine. The purified peptides were characterized by electrospray mass spectrometry, analytical HPLC and amino acid analysis. Binding was investigated using membranes prepared from either SMS-KAN or SK-N-MC cells. The activity of each Ala-NPY analogue was assessed in mucosal preparations of rat jejunum, where NPY and PYY exert antisecretory responses which are Y2-like in pharmacology. Fourteen analogues with L-alanine replacements at position 3, 5, 8, 13, 20, 21, 22, 26, 27, 28, 29, 30, 34 and 36 were selected, none of which exhibited any antagonism of NPY responses. An order of agonist potency showed [Ala3] NPY and [Ala30] NPY equipotent with NPY, a 4-20-fold loss of activity with [Ala5] NPY, [Ala13] NPY, [Ala20] NPY, [Ala21] NPY and [Ala22] NPY; a 50-100-fold loss of activity, [Ala8] NPY, [Ala27] NPY, [Ala28] NPY and [Ala36] NPY, while [Ala34] NPY was inactive. This structure-activity relationship is similar to, but not the same as that observed in Y2-expressing SMS-KAN cells.

Amino Acid Sequence↗
PubMed1997

Inhibition of cyclic AMP-dependent chloride secretion by PP receptors and alpha 2-adrenoceptors in a human colonic epithelial cell line.

The effects of a number of agonists which inhibit intestinal chloride secretion were investigated in Colony-1 (Col-1) cells, a subpopulation derived from the HCA-7 human adenocarcinoma cell line. Neither peptide YY (PYY) or somatostatin 14-28 (SRIF) reduced short-circuit current (SCC) in Col-1 epithelial layers stimulated with vasoactive intestinal polypeptide (VIP), suggesting that their respective receptors are either absent in this cell line, or are not functionally coupled. A second member of the neuropeptide Y family, pancreatic polypeptide (PP), decreased VIP-elevated SCC with an EC50 of 25.6 nM. Maximal PP responses were unaffected by prior addition of PYY, indicating that Col-1 cells may express a PP specific, Y4-like receptor. The alpha 2-adrenoceptor agonist clonidine also attenuated VIP-stimulated SCC (EC50342 nM) through the alpha 2A receptor subtype, since clonidine responses were inhibited by yohimbine and rauwolscine but not altered by previous addition of prazosin. Col-1 cells responded to both apical and basolateral addition of VIP or clonidine; to an extent, this lack of sidedness reflects the ability of drugs to permeate through the Col-1 epithelial layers. Both PP and clonidine also inhibited SCC in unstimulated Col-1 cells or those pretreated with 3-isobutyl-1-methylaxanthine (IBMX) or a submaximal concentration of forskolin, agents which both directly elevate intracellular cAMP. After a maximal concentration of forskolin (10 microM), which increased SCC to a significantly greater extent than either VIP or IBMX, the effects of both agonists were negligible. The absence of PP and clonidine responses under these conditions may have implications for the mechanisms by which these agonists inhibit, chloride secretion in Col-1 epithelia. In addition carbachol reduced SCC stimulated by 10 microM forskolin, in contrast to control carbachol responses which consisted of a rapid decrease followed by a transient elevation in SCC; this observation suggests that Col-1 cells may also be a useful model for studying the interactions between Ca(2+)- and cAMP-dependent mechanisms involved in epithelial ion transport.

Adenocarcinoma↗
PubMed1997

Disaster relief work: nurses and others in bushfire territory.

This paper describes one aspect of a study into the experiences in long-term healing of a community following the 1983 Ash Wednesday bushfire. Forty participants were interviewed, of whom 26 were residents and 14 disaster relief workers. The paper concentrates on the experiences of the latter, describing how they came to understand the bushfire affected the community and how they managed disaster work. For novices it was a profoundly difficult experience, for which they received little help and had to manage with whatever skill they drew on in their 'normal' working lives, mixed with a good deal of intuition. The paper suggests that health workers in vulnerable areas require preparation for a likely disaster; that 'outsiders' need to deal through existing community groups and individuals to gain access to those in need of their skills, and that they also require preparation for helping 'insiders' who are themselves victims of the catastrophe.

Adaptation, Psychological↗
PubMed1996

Selective inhibition of neuropeptide Y Y1 receptors by BIBP3226 in rat and human epithelial preparations.

BIBP3226 (N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-D-arginine amide) has been used to examine the presence of neuropeptide Y Y1 receptors in 3 gastrointestinal epithelial preparations, namely the rat jejunum and descending colon mucosae and a human colonic adenocarcinoma cell line. The selective Y1 receptor antagonist (1 microM BIBP3226) had no significant effect upon either peptide YY (PYY) responses or on electric field stimulated changes in electrogenic ion transport in rat jejunum mucosa. Partial inhibition of PYY responses was observed following BIBP3226 pretreatment of rat colon mucosal preparations in the presence and absence of tetrodotoxin. Responses to the Y1 selective agonist [Leu31,Pro34]neuropeptide Y ([Leu31, Pro34]NPY) in descending colon preparations were significantly attenuated by BIBP3226 (1 microM). The same concentration of antagonist abolished responses to PYY and [Leu31,Pro34]NPY but had no effect upon human pancreatic polypeptide (hPP) in monolayer cultures of the human adenocarcinoma cell line, Colony-6. Schild analysis of BIBP3226 antagonism of PYY responses in Colony-6 cells provided a pA2 value of 7.9 with a Hill slope of 1.03, indicating competitive antagonism at these epithelial Y1 receptors.

Animals↗
PubMed1996

The gene encoding mouse intestinal trefoil factor: structural organization, partial sequence analysis and mapping to murine chromosome 17q.

Trefoil peptides, a growing family of secretory molecules, have been identified mainly in the gastrointestinal tract of humans, rodents and amphibians. In the present study, the nucleotide sequence of a large portion (81%) of the gene encoding murine intestinal trefoil factor (mITF) and its whole genomic organization were determined. The mITF gene contains three exons distributed over 5 kb of genomic DNA. The genomic sequence is highly conserved, as compared with that of the rat and human ITF, and contains several AP-1-binding sites, the consensus binding site for the transcription factor Sp1, and a sequence homologous to a heat-shock element. Fluorescence in situ hybridization was used to assign ITF to chromosome 17 of the murine genome, a region syntenic with the trefoil gene cluster on human chromosome 21q22.3.

Amino Acid Sequence↗
PubMed1996

Effects of pancreatic spasmolytic Polypeptide (PSP) on epithelial cell function.

Trefoil peptides are expressed near endodermal ulcerations and may modulate epithelial repair. The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats. Ion transport was assessed as changes in short-circuit current in rat intestine and adenocarcinoma cells in Ussing chambers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in the presence of extracellular glutathione (GSH). The effect was attenuated by GSH depletion with buthionine sulphoximine, even in GSH-containing media. When GSH-reduced PSP was carboxymethylated with iodoacetic acid, it still depended on extracellular GSH for its growth effect. Intestinal epithelial proliferation in rats was not affected by either intravenous or intraluminal infusion. PSP had no effect on basal or stimulated ion flux in rat jejunum or epithelial monolayers. The peptide did not compete with 125I-labeled epidermal growth factor for its receptor. [14C]Iodoacetamide treatment of PSP, followed by prolonged tryptic digestion yielded predominantly a 14C-labeled tetrapeptide fragment containing Cys1O4, with a lesser quantity of a 14C-labeled 15-amino-acid peptide containing Cys95 (molar ratio 15:1). GSH may predominantly reduce the Cys6-Cys1O4 terminal disulphide bond in PSP. We conclude that some epithelia may exhibit a growth response to PSP if extracellular GSH is present. Reduction of PSP by GSH is not necessary for this response, suggesting that the trefoil receptor or its signal transduction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concentration.

Animals↗
PubMed1996

The functional investigation of a human adenocarcinoma cell line, stably transfected with the neuropeptide Y Y1 receptor.

1. The human adenocarcinoma cell line, HT-29, has been stably transfected with the cDNA sequence for the rat neuropeptide Y (NPY) Y1 receptor, and three Y1 clones (Y1-4, Y1-7 and Y1-16) have been isolated which express high levels of specific [125I]-PYY binding. We have studied the functional responses or lack of responses to peptide YY (PYY) and its analogues in the three transfected clones and HT-29 wild type (wt) cells. 2. Vasoactive intestinal polypeptide (VIP) produced long-lasting increases in short-circuit current (SCC) in both HT-29 wt cells and the Y1 clones. VIP EC50 values were 8.4-11.7 nM in all four cases. The elevation in SCC after a maximal concentration of VIP (30 nM) was significantly greater in Y1-7 cells than in either HT-29 wt epithelia or the other Y1 cell lines. 3. PYY (100 nM) and human pancreatic polypeptide (hPP; 1 microM) were ineffective in HT-29 wt cells under either basal or stimulated conditions. In contrast, basolateral additions of PYY reduced both basal and VIP-stimulated SCC in all three Y1 clones. After VIP, the PYY EC50 values (in nM) were 18.6 in Y1-4, 8.0 in Y1-7 and 52.5 in Y1-16 hPP (1 microM) produced only small and transient responses in each transfected cell type. 4. The Y1 receptor agonist, [Leu31, Pro34] NPY (1 microM) was also effective in the three Y1 cell lines. In the Y1-7 clone the EC50 value for the effect of this peptide was 149 nM, 18.6 fold less potent than PYY. 5. PYY and the Y1-selective non-peptide antagonist, BIBP 3226 displaced [125I]-PYY binding from Y1-7 cell membranes with Ki values of 2.0 and 3.1 nM respectively. In the Y1-7 clone, BIBP 3226 fully inhibited the reductions in VIP-stimulated SCC induced by 30 nM PYY, with an IC50 of 27.2 nM and 30 nM BIBP 3226 caused a parallel rightward shift on the PYY concentration-response curve, with an approximate pKB of 8.0. 6. HT-29 clones stably expressing the Y1 receptor therefore show responses to PYY and its analogues that are characteristic of that subtype, and the Y1-7 clone in particular will be useful in the assessment of novel Y1-specific drugs. This approach will also allow the functional study of NPY Yi receptors with selected mutations.

Adrenergic alpha-Agonists↗
PubMed1995

Immunoprecipitation and characterization of a binding protein specific for the peptide, intestinal trefoil factor.

Recombinant rat intestinal trefoil factor (rITF) and human spasmolytic polypeptide (hSP) were irreversibly cross-linked to specific binding sites in solubilized rat intestinal epithelial membranes and human adenocarcinoma cells. Analysis of the immunoprecipitates by immunoblotting identified a cross-linked protein complex of approximately 45 kDa, which under reducing conditions appeared as a approximately 28-kDa band and the latter displayed ligand-stimulated phosphorylation of a tyrosine, but not a threonine or serine, residue in the binding complex. [125I]rITF was used to localize binding sites by autoradiography of frozen sections from rat gastrointestinal tissues. A high density of specific [125I]rITF binding sites was present within gastric, colonic, and jejunal mucosal glands. Unlabeled hSP partially inhibited [125I]rITF binding at a concentration of 1 microM when compared with the same concentration of unlabeled rITF. These studies support earlier observations for the existence of trefoil binding sites in the gastrointestinal tract and further suggest that hSP has affinity for the mucosal rITF binding site.

Animals↗
PubMed1995

Glutaraldehyde concentration in the sterilization of endoscopes.

Controversy over appropriate disinfection of endoscopes continues with the most commonly utilized solution in Australian hospitals, despite concern over its efficacy, being 1% glutaraldehyde (AIDAL). Review of the in-use concentrations of glutaraldehyde at Princess Alexandra Hospital has documented a significant dilutional effect in 1% glutaraldehyde by gastrointestinal endoscopes. Each hospital should determine the minimum in-use concentration acceptable for any given disinfecting solution and any given range of endoscopes. Once this level is reached, a solution change should routinely occur. Such decisions can only be made by regularly monitoring in-use concentrations of disinfectants.

Disinfectants↗
PubMed1995

Modulation of epidermal growth factor effects on epithelial ion transport by intestinal trefoil factor.

1. The direct epithelial effects of epidermal growth factor (EGF) and its modulation by intestinal trefoil factor (ITF) have been studied in a human colonic adenocarcinoma cell line called Colony-29 (Col-29). 2. When grown in culture as confluent monolayers and voltage-clamped in Ussing chambers, these epithelia responded with an increase in short circuit current (SCC) to basolateral as well as to apically applied EGF although the latter responses (at 10 nM) were only 25% of those observed following basolateral peptide. 3. Recombinant rat ITF (added to the basolateral surface) did not alter basal SCC levels, but it did enhance the electrogenic effects of basolateral EGF. The EC50 values for EGF-induced ion transport were 0.25 nM in control, and 0.26 nM in ITF pretreated Col-29 epithelia. A significant increase in the size of EGF responses (0.1 nM-10 nM) was observed in the presence of 10 nM ITF and the half-maximal concentration for this modulatory effect of ITF was 7.6 nM. 4. The EGF-induced increases in SCC were partially inhibited (50%) by piretanide pretreatment, indicating that Cl- secretion is involved. EGF responses either in the presence or absence of ITF were also significantly reduced (84% and 66% respectively) by the cyclo-oxygenase inhibitor, piroxicam, therefore implicating prostaglandins as mediators of EGF-stimulated anion secretion. 5. We conclude that in confluent Col-29 epithelia, basolateral EGF stimulates a predominantly prostaglandin-dependent increase in Cl- secretion that is enhanced by basolateral ITF, and that these two peptides may interact in normal and damaged mucosa to alter the local apical solute and fluid environment.

Animals↗
PubMed1995

Functional characterization of receptors with affinity for PYY, NPY, [Leu31,Pro34]NPY and PP in a human colonic epithelial cell line.

1. Confluent epithelial layers of a human adenocarcinoma cell line called Colony-6 have been shown to respond to nanomolar concentrations of vasoactive intestinal polypeptide (VIP), peptide YY (PYY), neuropeptide Y (NPY) and somatostatin (Som). 2. The VIP-induced increase in basal short-circuit current (SCC) was attenuated by basolateral application of Som, PYY or NPY, and also by the Y1-receptor agonist [Leu31,Pro34]NPY, as well as pancreatic polypeptide (PP). High concentrations (0.1-3.0 microM) of NPY(2-36) were effective but the C-terminal fragment NPY(13-36) (0.1-1.0 microM) and desamidoNPY (0.6 microM) were not active. A rank order of agonist EC50 values was: PYY > NPY > [Leu31,Pro34]NPY > PP > NPY(2-36) >> NPY (13-36). 3. Receptors for all these peptides were preferentially located within the basolateral domain. Apical addition of PP (1 microM) and Som (100 nM) had no effect upon basal SCC while apical VIP (10 nM) responses were 18%, and apical PYY (100 nM) were 27% the size of respective basolateral controls (100%). 4. Cross-desensitization was observed between [Leu31,Pro34]NPY (1 microM) and both PYY (100 nM) and PP (1 microM) and between PYY and NPY(2-36) (1 microM), but was not significant between PYY (100 nM) and PP (1 microM). We suggest that either these cells express a single new Y-receptor with an unusual phenotype or that two Y-receptor populations exist in Colony-6 cells.

Adenocarcinoma↗