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Biomedical subjects

C J Small

Publications and source records attributed to C J Small.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hypothalamic localization of the feeding effect of agouti-related peptide and alpha-melanocyte-stimulating hormone.

The melanocortin-4 receptor (MC4R) in the hypothalamus is thought to be important in physiological regulation of food intake. We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous MC4R agonist, and agouti-related peptide (Agrp), an endogenous MC4R antagonist. Cannulae were inserted into the rat hypothalamic paraventricular (PVN), arcuate (Arc), dorsomedial (DMN), and ventromedial (VMN) nuclei; the medial preoptic (MPO), anterior hypothalamic (AHA), and lateral hypothalamic (LHA) areas; and the extrahypothalamic central nucleus of the amygdala (CeA). Agrp (83-132) (0.1 nmol) and [Nle4, D-Phe7]alpha(-MSH (NDP-MSH) (0.1 nmol), a stable alpha-MSH analog, were administered to fed and fasted rats, respectively. The PVN, DMN, and MPO were the areas with the greatest response to Agrp and NDP-MSH. At 8 h postinjection, Agrp increased feeding in the PVN by 218 +/- 23% (P < 0.005), in the DMN by 268 +/- 42% (P < 0.005), and in the MPO by 236 +/- 31% (P < 0.01) compared with a saline control group for each nucleus. NDP-MSH decreased food intake in the PVN by 52 +/- 6% (P < 0.005), in the DMN by 44 +/- 6% (P < 0.0001), and in the MPO by 55 +/- 6% (P < 0.0001) at 1 h postinjection. Injection into the AHA and CeA resulted in smaller alterations in food intake. No changes in feeding were seen after the administration of Agrp into the Arc, LHA, or VMN, but NDP-MSH suppressed food intake in the Arc and LHA. This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect on feeding.

Agouti-Related Protein↗
PubMed2000

Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

Animals↗
PubMed1999

Investigation of the feeding effects of melanin concentrating hormone on food intake--action independent of galanin and the melanocortin receptors.

Melanin concentrating hormone (MCH) is recognised as a hypothalamic appetite stimulant. The mechanism of action of MCH is undetermined largely due to lack of identification of hypothalamic MCH receptors. We designed in vivo and in vitro studies to further characterise the feeding effects of MCH in the rat. MCH was injected directly into the paraventricular nucleus (PVN) at the beginning of the light phase. PVN MCH (0.5 microg) produced an increase in 2 h food intake of 272+/-60% vs. saline control (0.7+/-0.2 g), p<0.05. The time course of the effect of intracerebroventricular (i.c.v.) administration of 5 microg MCH on food intake was investigated. An increase in feeding was observed within 15 min from the time of injection and was not sustained beyond half an hour following administration. To investigate a possible interaction with galanin, 5 microg of MCH was injected i.c.v. with or without 10 microg of galanin. The two peptides together increased 1 h feeding above that of either peptide alone, 768+/-62% (compared with the saline group, 0.47+/-0.2 g), p<0.05 vs. 585+/-36%, galanin alone and 317+/-72%, MCH alone. Finally, to investigate if MCH bound to the brain melanocortin receptors, receptor autoradiography was performed on rat brain sections with the stable analogue of alpha MSH, [125I] Nle(4), D-Phe(7)-alphaMSH and unlabeled MCH. MCH did not compete with [125I] Nle(4), D-Phe(7)-alphaMSH binding. Results demonstrate that MCH stimulates feeding via the PVN, has a short onset and duration of action and activates feeding by mechanisms independent to galanin and the melanocortin receptors.

Animals↗
PubMed1999

Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat.

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.

Animals↗
PubMed1998

Targeted disruption of the murine galanin gene.

The 29 amino acid neuropeptide galanin is widely distributed in the nervous and endocrine systems; highest levels of galanin synthesis and storage occur within the hypothalamus in the median eminence, but it is also abundantly expressed in the basal forebrain, the peripheral nervous system, and gut. To further define the role played by galanin in the peripheral nervous and endocrine systems, a mouse strain carrying a loss-of-function germ-line mutation of the galanin locus, engineered by targeted mutagenesis in embryonic stem cells, has been generated. The mutation removes the first five exons containing the entire coding region for the galanin peptide. Germ-line transmission of the disrupted galanin locus has been obtained, and the mutation has been bred to homozygosity on the inbred 129O1aHsd background. Phenotypic analysis of mice lacking a functional galanin gene demonstrate that these animals are viable, grow normally, and can reproduce. A marked reduction in both the anterior pituitary prolactin content and in circulating plasma levels of the hormone is evident. Lactation is abolished along with abrogation of the proliferative response of the lactotroph to estrogen. The responses of sensory neurons to injury in the mutants are markedly impaired. Peripheral nerve regeneration is reduced with associated long-term functional deficits. There is a striking reduction in the development of chronic neuropathic pain. These two phenotypic changes may be explained, in part, by the observation that a subset of dorsal root ganglion neurons is lost in the mutant animals, implying a role for galanin as a trophic cell survival factor. These initial findings have important implications for our understanding and potential therapeutic treatment of (a) sensory nerve regeneration and neuropathic pain and (b) disordered pituitary proliferation and the development of prolactinoma.

Amino Acid Sequence↗
PubMed1998

Galanin regulates prolactin release and lactotroph proliferation.

The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of estradiol-17beta induces pituitary hyperplasia followed by adenoma formation and causes a 3,000-fold increase in the galanin mRNA content of the lactotroph. To further study the role of galanin in prolactin release and lactotroph growth we now report the generation of mice carrying a loss-of-function mutation of the endogenous galanin gene. There is no evidence of embryonic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolactin. Pituitary prolactin message levels and protein content of adult female mutant mice are reduced by 30-40% compared with wild-type controls. Mutant females fail to lactate and pups die of starvation/dehydration unless fostered onto wild-type mothers. Prolactin secretion in mutant females is markedly reduced at 7 days postpartum compared with wild-type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regulate prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts as a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.

Alleles↗
PubMed1998

Neuropeptide Y (NPY) actions on the corticotroph cell of the anterior pituitary gland are not mediated by a direct effect.

Neuropeptide Y has been implicated in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, the regulation of growth and sexual function, and is the most potent stimulant of feeding yet reported. The actions of NPY on the HPA axis are thought to be mediated via an activation of the corticotrophin releasing hormone (CRH) neurones within the paraventricular nucleus of the hypothalamus. The ability of NPY to directly influence the corticotroph cell is currently controversial. These studies investigated whether NPY could have a direct influence on anterior pituitary adrenocorticotrophic hormone (ACTH) release. In dispersed male rat anterior pituitary cells, NPY (1-1000 nM) had no effect on either basal or CRH (1 nM) stimulated ACTH release. Basal release, NPY (1000 nM) 111 +/- 6% vs. control 103 +/- 5%. CRH stimulated release, CRH (1 nM) with NPY (1000 nM) 226 +/- 23% vs. CRH (1 nM) alone 228 +/- 20%. In addition, NPY (1000 nM) had no effect on either basal or CRH (1 nM) stimulated ACTH release in the mouse corticotroph cell line, AtT-20. Thus, in two models of the anterior pituitary corticotroph NPY had no effect on ACTH release. NPY induced activation of the HPA axis is likely to be mediated via a modulation of hypothalamic CRH and not via a direct action at the level of the anterior pituitary.

Adrenocorticotropic Hormone↗
PubMed1998

The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism.

We have previously shown that intracerebroventricular BIBP 3226 inhibits NPY induced feeding in rats. However, this was associated with abnormal behaviour, likely to be due to interaction with Y1 receptors involved in mechanisms other than the control of food intake. In order to minimise such interactions we investigated the effects of paraventricular nucleus (PVN) injections of BIBP 3226 and its inactive enantiomer BIBP 3435. Intra-PVN injection of NPY (0.1-2.5 nmol/animal) increased food intake, with an EC50 of approximately 0.15 nmol/animal. Injections of BIBP 3226 and BIBP 3435 (0.25-25 nmol) reduced NPY-induced food intake in a dose responsive manner, with BIBP 3226 reducing food intake by 95%, and BIBP 3435 by 65% at the highest dose tested. The reversibility of the effect of BIBP 3226 was investigated by measuring the feeding response to NPY (0.5 nmol) in animals 1 week after BIBP 3226 injection. The response to NPY was less in animals which had received high doses of BIBP 3226. Animals previously injected with saline vehicle alone showed a normal NPY feeding response. These results suggest that BIBP 3226 may be inhibiting NPY-induced food intake in a non-specific manner, not secondary to inhibition of the Y1 receptor. This does not, however rule out a role for the Y1 receptor in the control of food intake by NPY.

Animals↗
PubMed1998

Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line.

To examine the influence of the putative satiety factor (GLP-1) on the hypothalamo-pituitary-gonadal axis, we used GT1-7 cells as a model of neuronal luteinizing hormone- releasing hormone (LHRH) release. GLP-1 caused a concentration-dependent increase in LHRH release from GT1-7 cells. Specific, saturable GLP-1 binding sites were demonstrated on these cells. The binding of [125I]GLP-1 was time-dependent and consistent with a single binding site (Kd = 0.07+/-0.016 nM; binding capacity = 160+/-11 fmol/mg protein). The specific GLP-1 receptor agonists, exendin-3 and exendin-4, also showed high affinity (Ki = 0.3+/-0.05 and 0.32+/-0.06 nM, respectively) as did the antagonist exendin-(9-39) (Ki = 0.98+/-0.24 nM). At concentrations that increased LHRH release, GLP-1 (0.5-10 nM) also caused an increase in intracellular cAMP in GT1-7 cells (10 nM GLP-1: 7.66+/-0.4 vs. control: 0.23+/-0.02 nmol/mg protein; P < 0.001). Intracerebroventricular injection of GLP-1 at a single concentration (10 microg) produced a prompt increase in the plasma luteinizing hormone concentration in male rats (GLP-1: 1.09+/-0.11 vs. saline: 0.69+/-0.06 ng/ml; P < 0.005). GLP-1 levels in the hypothalami of 48-h-fasted male rats showed a decrease, indicating a possible association of the satiety factor with the low luteinizing hormone levels in animals with a negative energy balance.

Animals↗
PubMed1998

Galanin is a paracrine inhibitor of gonadotroph function in the female rat.

Recent evidence suggests that pituitary galanin synthesized in the lactotroph is a paracrine regulator of lactotroph proliferation and PRL secretion and that these effects are mediated via a pituitary-specific galanin receptor, GAL-R2(orig.). At this receptor subtype, the galanin fragment 3-29 is fully active, in contrast to both the cloned GAL-R1 and GAL-R2, at which this fragment is inactive. Since paracrine communication has been demonstrated between pituitary gonadotrophs and lactotrophs, we investigated the hypothesis that galanin is also a paracrine regulator of gonadotroph function. Galanin attenuated LHRH-stimulated LH release in a dose-dependent manner in monodispersed rat anterior pituitaries harvested at proestrus (LHRH 100 nM, 10.7 +/- 0.2 ng/ml(-1) x 4 h vs. LHRH 100 nM + 1 microM porcine galanin (pGal), 7.0 +/- 0.2 ng/ml(-1) x 4 h; P < 0.01; i.e. 37% reduction). Galanin had similar suppressive effects on FSH release. Galanin, also dose-dependently, attenuated the LHRH-stimulated LH release from perifused proestrous rat pituitary fragments. pGal (1 microM) reduced the stimulated LH release by 80%, [area under the curve (AUC), LHRH 100 nM, 713 +/- 149 vs. LHRH 100 nM + 1 microM pGal, 131 +/- 7 ng/min x ml(-1) x 4 h; P < 0.02]. In addition, galanin 3-29, the specific GAL-R2(orig.) receptor agonist, inhibited LHRH-stimulated LH release from perifused proestrous rat pituitary fragments [AUC, LHRH 100 nM, 642 +/- 77 ng/min x ml(-1) vs. LHRH 100 nM + pGal 1-29, 206 +/- 44 ng/min x ml(-1) (P < 0.02); and LHRH 100 nM + pGal 3-29, 310 +/- 19 ng/min x ml(-1) (P < 0.02)]. Immunoblockade with specific galanin antiserum potentiated the LHRH-stimulated release of LH by 48% from perifused proestrous rat pituitary fragments (AUC, LHRH 100 nM + galanin antiserum, 721 +/- 65 ng/min x ml(-1) vs. LHRH 100 nM alone or with nonimmune antiserum, 489 +/- 33 ng/min x ml(-1) or 545 +/- 46 ng/min x ml(-1), P < 0.05). This data suggests that galanin may act as a paracrine agent via the pituitary-specific GAL-R2(orig.) to inhibit gonadotroph function.

Animals↗
PubMed1998

A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo.

Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, p<0.05). The hyperphagia was similar to that seen when 1 nmol of the synthetic MC3-R and MC4-R antagonist SHU9119 was given i.c.v. (19.6+/-1.8 g saline vs 32.5+/-1.7 g SHU9119, p<0.001). Both Agrp(83-132) and SHU9119 blocked the reduction in 1-h food intake of i.c.v. alphaMSH at the beginning of the dark phase. This effect occurred independently of whether the antagonists were administered simultaneously, or nine hours prior, to the alphaMSH. We have also shown Agrp(83-132) is an antagonist at the MC3-R and MC4-R, with similar inhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.

Agouti Signaling Protein↗
PubMed1997

Peptide analogue studies of the hypothalamic neuropeptide Y receptor mediating pituitary adrenocorticotrophic hormone release.

Hypothalamic neuropeptide Y (NPY) is thought to be important in the regulation of feeding and also in the release of Adrenocorticotrophic hormone (ACTH). Intracerebroventricular administration of NPY to male rats significantly increased plasma ACTH 10 min after injection and stimulated 2-h food intake. A series of analogues of NPY that have a greatly reduced affinity for the Y1 [human pancreatic polypeptide (human PP), NPY(3-36)], the Y2 ([Pro34]NPY, human PP), the Y3 (peptide YY), and the Y6 (human PP) receptor, all markedly stimulated ACTH release. Rat PP, which binds with high affinity to the Y4 receptor, was unable to stimulate ACTH release. A novel analogue fragment [Pro34]NPY(13-36) was synthesized as a ligand with low Y1 and Y2 receptor affinity. Interestingly, neither [Pro34]NPY(13-36) nor the selective Y5 receptor agonist [D-Trp32]NPY stimulated food intake, whereas both significantly increased plasma ACTH. Thus the hypothalamic NPY receptor mediating increases in plasma ACTH has a fragment activation profile unlike the Y1-Y4 or Y6 receptors and appears distinct from the NPY receptor controlling food intake.

Adrenocorticotropic Hormone↗
PubMed1997

Neuropeptide Y induced feeding in the rat is mediated by a novel receptor.

There are now six recognized neuropeptide Y (NPY) receptor subtypes (Y1-Y4 and two recently cloned distinct receptors labeled Y5), of which Y1 and one of the Y5's have been suggested could mediate the effect of NPY on feeding. The fragments NPY(2-36) and NPY(3-36), which bind Y1 only poorly, were injected intracerebroventricularly (icv) and found to have similar dose-response relationships to NPY in the stimulation of feeding. However NPY (13-36), which stimulates both Y2 and Y5, caused no increase in food intake, even at high doses. Maximal stimulation with the classical Y1 agonist [Pro34]-NPY produced only 50% of the maximum effect of NPY itself despite fully inhibiting adenylyl cyclase activity in vitro in a Y1 system. The novel fragment [Pro34]-NPY(3-36) is as effective at stimulating food intake as the classical Y1 analogue [Pro34]-NPY but bound to the Y1 receptor with only 1/20th of the affinity of NPY and failed to inhibit adenylyl cyclase through this receptor. [Pro34]-NPY(3-36) is therefore a relatively appetite-selective ligand. Coadministration of high dose NPY(13-36) and [Pro34]NPY did not enhance feeding compared with [Pro34]-NPY alone. In addition, the NPY Y1 receptor antagonist BIBP-3226, which does not bind Y2, Y4, or Y5 receptors, significantly reduced NPY induced feeding. These results indicate that the feeding effect of icv NPY involves a novel receptor and that it is functionally distinct from the recognized receptor subtypes.

Adenylyl Cyclases↗
PubMed1997

Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study.

Adrenomedullin has been proposed to be a circulating hormone regulating systemic and pulmonary blood pressure. A potential therapeutic role in the management of pulmonary hypertension has been suggested based on animal studies, but the pharmacokinetics and pharmacodynamics in human subjects have not been studied. We have infused adrenomedullin into volunteers at 3.2 pmol/kg.min, which more than quadrupled (52 pmol/L) normal circulating concentrations. At this dose no change in heart rate or blood pressure was noted. When infused at 13.4 pmol/kg.min to achieve a concentration over 40 times normal circulating levels (448 pmol/L), there was a significant fall in diastolic blood pressure from 69 +/- 2 to 53 +/- 2 mm Hg and a significant increase in pulse rate from 57 +/- 3 to 95 +/- 4 beats/min. Circulating PRL concentrations rose from 197 +/- 46 to 372 +/- 64 IU/L (mean +/- SEM; P < 0.01). No effect was seen on ACTH, TSH, FSH, LH, or cortisol. When the infusion was discontinued, baseline pulse and blood pressure were reestablished after 20 min. Adrenomedullin has a MCR of 27.4 +/- 3.6 mL/kg.min, with a circulating half life of 22 +/- 1.6 min and an apparent volume of distribution of 880 +/- 150 mL/kg. Column chromatography of plasma taken during infusion and decay of adrenomedullin showed no evidence of the production of additional molecular forms. These results are consistent with a peptide that is markedly tissue bound. Plasma adrenomedullin concentrations were increased in patients with renal impairment (14.1 +/- 0.9 pmol/L) compared to those in healthy volunteers (8.1 +/- 0.7 pmol/L), with a good correlation (r = 0.86) between circulating adrenomedullin and plasma creatinine. The circulating concentration of adrenomedullin necessary to affect blood pressure greatly exceeds that observed in healthy volunteers and in patients with a range of pathological conditions. Thus, adrenomedullin may be a paracrine regulator of vascular smooth muscle in humans.

Adrenomedullin↗
PubMed1996

Glucagon-like peptide-1 (GLP-1) releases thyrotropin (TSH): characterization of binding sites for GLP-1 on alpha-TSH cells.

We have demonstrated specific binding sites for [125I]glucagon-like peptide 1 (GLP-1) on membranes from the rodent thyrotrope cell line, alpha-TSH. Specific [125I]GLP-1 binding was saturable and time dependent. Equilibrium saturation binding analysis was consistent with the presence of a single class of binding site (binding capacity, 85 +/- 7 fmol/mg protein) with a dissociation constant (Kd) of 28 +/- 13 pM. The specific GLP-1 receptor agonists, exendin-4 and exendin-3, and the antagonist, exendin-(9-39), bound to the receptor sites with high affinity (Ki = 190 +/- 70 pM; 130 +/- 50 and 1200 +/- 470 pM, respectively). Chemical cross-linking of [125I]GLP-1-receptor complexes revealed a single band of 64,300 +/- 100 Mr in alpha-TSH membranes. In addition, specific PCR studies demonstrated the presence of GLP-1 receptor messenger RNA. Binding of the peptide to alpha-TSH cell membranes resulted in increased intracellular cAMP concentrations (10 nM GLP-1, 1010 +/- 83 pmol/10(6) cells.h; control, 175 +/- 60 pmol/10(6) cells.h; P < 0.002), indicating that the receptor is linked to stimulation of adenylyl cyclase. GLP-1-mediated increases in cAMP were inhibited by exendin-(9-39) in a dose-dependent manner. Furthermore, GLP-1 stimulates basal TSH release from dispersed anterior pituitary cells in a concentration-dependent manner (100 nM GLP-1, 63 +/- 3 fmol/10(6) cells.h; control, 35 +/- 1 fmol/10(6) cells.h; P < 0.0005), but had no effect on basal PRL, GH, or LH release.

Animals↗
PubMed1985

No demonstrable relationship between IgM and IgG antinuclear antibody levels and acetylator phenotype in patients with systemic lupus erythematosus.

To ascertain the possible influence of acetylator phenotype on antinuclear antibodies in systemic lupus erythematosus (SLE), we assayed sera from 11 rapid acetylators and 10 slow acetylators for IgM and IgG antibodies to chromatin, histones, denatured DNA, and native DNA. Whereas the majority of SLE patients of both acetylator phenotypes had elevated levels of antibodies to all 4 antigens compared with normal controls, there was no difference in antibody activities between slow acetylator patients versus rapid acetylator patients for these antigens. We conclude that levels of antibody to chromatin, histones, and DNA in SLE patients are similar irrespective of acetylator phenotype, and that if a protective effect of slow acetylation on spontaneous development of antinuclear antibodies does occur, a prospective study of presymptomatic individuals at high risk for lupus may be required to reveal this effect.

Acetylation↗