Broiler performance and in vivo viscosity as influenced by a range of xylanases, varying in ability to effect wheat in vitro viscosity.

1. Exogenous enzymes such as xylanase are used in diets for broilers to eliminate anti-nutritive effects caused by the presence of non-starch polysaccharides (NSP). It has been proposed that the mechanism by which xylanases exert their effect is through reducing in vivo viscosity within the broiler digestive tract. Previous research has reported that in vitro viscosity was a reasonable predictor of in vivo viscosity and that this method could be used to assess the efficacy of xylanases. 2. The objective of this study was to examine the response of broilers offered a wheat-based diet supplemented with a range of xylanases, varying in ability to reduce in vitro viscosity. 3. A total of 18 xylanases (Syngenta Animal Nutrition) were used to investigate the effect of xylanase on wheat in vitro viscosity. For the in vitro viscosity assay, pepsin was dissolved in either 005 or 01 M hydrochloric acid (HCl). 4. A wheat-based diet was formulated, produced and split into 7 batches; xylanase (500 U/kg) was sprayed onto 6 of the batches and the 7th was the control. This was repeated three times to produce a total of 21 diets, 18 of which contained xylanase. 5. The experiment was conducted in three consecutive trials. Each trial utilised 63 male, Ross broilers from 7 to 28 d of age. Dry matter intake (DMI), liveweight gain (LWG) and gain:feed were determined weekly. Excreta were collected from d 14 to 21 for determination of apparent metabolisable energy (AME). Oil and neutral detergent fibre (NDF) digestibility and ileal digestibility of dry matter (DM) and starch were determined. 6. Regression analyses were applied to the mean intestinal viscosity against DMI, LWG, gain:feed and the ratio of metabolisable energy to gross energy (ME:GE). To compare xylanases across the three trials, the data were subjected to REML analysis (Genstat 5). 7. When 01 M HCl was used for dissolution of pepsin, considerable reductions in in vitro viscosity were achieved for the majority of the xylanases-to values less than 12% of the control treatment. When 005 M HCl was used for the dissolution of pepsin, initial viscosity values were lower and the reduction in in vitro viscosity less dramatic than that observed with 01 M HCl. 8. With the exception of diets containing xylanases 9003 and 7162, significant reductions in in vivo viscosity were observed for diets containing xylanase in comparison to the control diet. 9. In terms of gain:feed, ME:GE and AME the xylanases ranked best were 2230 and 9003. Xylanase 2230 also resulted in the highest values for ileal DM and starch digestibility. 10. There were weak but significant relationships between in vitro viscosity and in vivo jenjunal digesta viscosity when in vitro viscosity was determined using either 01 or 005 M HCl (r(2)= 0287 and 0240, respectively). 11. The relationship between jejunal viscosity and DMI was significant (P < 005) but relatively poor (r(2)= 023). There were also significant (P < 005) relationships between jejunal digestal viscosity and gain:feed and ME:GE (r(2)= 034 and 028, respectively). 12. In conclusion, in vitro viscosity may be of some use in predicating xylanase response in vivo.

Fumaric and sorbic acid as additives in broiler feed.

The aim of the experiment was to study the effect of dietary organic acids, fumaric and sorbic, on nitrogen corrected apparent metabolisable energy (AME(N)), metabolisability of nutrients, endogenous losses and performance on young broiler chickens. A total of 56 male Ross broilers were used in a growing experiment from 14 to 30d age. Seven experimental wheat-based (655g/kg) diets were formulated. The control diet did not contain organic acids. The other six diets were produced with the addition of fumaric or sorbic acids, replacing 0.5% , 1.0% or 1.5% of the wheat. The organic acid supplemented diets contained higher levels of AME(N) compared to the control diet. Overall, birds offered organic acids had lower feed intake. Dietary organic acids did not significantly affect weight gain or feed efficiency, however, birds offered supplemented diets had lower numbers of Lactic acid bacteria and Coliforms in the ileum and caeca. Birds offered organic acids had lower levels of endogenous losses compared to control fed birds. There was a negative relationship between AME(N) of the diets and excreted endogenous losses, measured as sialic acid. It can be concluded that the decrease in secretions from the gastrointestinal tract in the presence of fumaric and sorbic acids may be a mechanism involved in the mode of action of dietary organic acids.

The feminisation of the orthodontic workforce.

OBJECTIVE: To describe the status and activity of women in the UK orthodontic workforce. DESIGN AND SETTING: Postal questionnaire based on the UK orthodontic workforce. SUBJECTS: All orthodontic providers in the UK. MATERIALS AND METHODS: A questionnaire was circulated to the total study population. The variables studied relating to sex were numbers, age, number of sessions worked, productivity, professional status and retirement intentions. RESULTS: The response rate was 72.7%. 31.4% of the participants were female. The average age of female providers was 42.7 (SE 0.48) years, who were on average 4 years younger than males. Sixty-six percent of specialist trainees are women and 34% men. 41.5% of male providers and 31.6% of female providers plan to retire in the next 15 years. The mean number of sessions worked by women was 7.2 (SE 0.1) and men 8.2 (SE 0.1). Women completed 24.2 (SE 1.9) cases per session and men 25.6 (SE 1.3). CONCLUSIONS: The orthodontic workforce is becoming increasingly feminised. The cumulative effect of more women completing fewer cases will mean that workforce planners will need to consider increasing numbers to allow for this feminisation.

Anti-proliferative effect of estrogen in breast cancer cells that re-express ERalpha is mediated by aberrant regulation of cell cycle genes.

Estrogen receptor (ER)-negative breast carcinomas do not respond to hormone therapy, making their effective treatment very difficult. The re-expression of ERalpha in ER-negative MDA-MB-231 breast cancer cells has been used as a model system, in which hormone-dependent responses can be restored. Paradoxically, in contrast to the mitogenic activity of 17beta-estradiol (E2) in ER-positive breast cancer cells, E2 suppresses proliferation in ER-negative breast cancer cells in which ERalpha has been re-expressed. We have used global gene expression profiling to investigate the mechanism by which E2 suppresses proliferation in MDA-MB-231 cells that express ERalpha through adenoviral infection. We show that a number of genes known to promote cell proliferation and survival are repressed by E2 in these cells. These include genes encoding the anti-apoptosis factor SURVIVIN, positive cell cycle regulators (CDC2, CYCLIN B1, CYCLIN B2, CYCLIN G1, CHK1, BUB3, STK6, SKB1, CSE1 L) and chromosome replication proteins (MCM2, MCM3, FEN1, RRM2, TOP2A, RFC1). In parallel, E2-induced the expression of the negative cell cycle regulators KIP2 and QUIESCIN Q6, and the tumour-suppressor genes E-CADHERIN and NBL1. Strikingly, the expression of several of these genes is regulated in the opposite direction by E2 compared with their regulation in ER-positive MCF-7 cells. Together, these data suggest a mechanism for the E2-dependent suppression of proliferation in ER-negative breast cancer cells into which ERalpha has been reintroduced.

Essential structural and functional determinants within the forkhead domain of FOXC1.

The forkhead domain (FHD)-containing developmental transcription factor FOXC1 is mutated in patients presenting with Axenfeld-Rieger malformations. In this paper, we report the introduction of positive, negative or neutral charged amino acids into critical positions within the forkhead domain of FOXC1 in an effort to better understand the essential structural and functional determinants within the FHD. We found that FOXC1 is intolerant of mutations at I87. Additionally, alterations of amino acids within alpha-helix 1 of the FOXC1 FHD affected both nuclear localization and transactivation. Amino acids within alpha-helix 3 were also found to be necessary for transactivation and can have roles in correct localization. Interestingly, changing amino acids within alpha-helix 3, particularly R127, resulted in altered DNA-binding specificity and granted FOXC1 the ability to bind to a novel DNA sequence. Given the limited topological variation of FHDs, due to the high conservation of residues, we anticipate that models of forkhead domain function derived from these data will be relevant to other members of the FOX family of transcription factors.

Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis.

BACKGROUND: Prostate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF-I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF-I in conjunction with endogenous IGF-I contributes to the osteoblastic phenotype characteristic of metastatic PC. METHODS: To test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines. RESULTS: Using RIA, we found serum-free conditioned media (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real-time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2. C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/- 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2 and C4-2B and at least equivalent protein expression. CONCLUSIONS: Our results suggest that PC cells that have metastasized to bone have an upregulated IGF-I regulatory system. This suggests an activated IGF-I axis contributes to the host-PC interaction in promoting osteoblastic metastases.

IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo.

IGF-I, a ubiquitous polypeptide, plays a key role in longitudinal bone growth and acquisition. The most predominant effect of skeletal IGF-I is acceleration of the differentiation program for osteoblasts. However, in vivo studies using recombinant human (rh) IGF-I and/or rhGH have demonstrated stimulation of both bone formation and resorption, thereby potentially limiting the usefulness of these peptides in the treatment of osteoporosis. In this study, we hypothesized that IGF-I modulates bone resorption by regulating expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) in bone cells. Using Northern analysis in ST2 cells, we found that human IGF-I suppressed OPG mRNA in a time- and dose-dependent manner: 100 micro g/LIGF-I (13 nM) decreased OPG expression by 37.0 +/- 1.8% (P < 0.002). The half maximal inhibitory dose of IGF-I was reached at 50 micro g/liter ( approximately 6.5 nM) with no effect of IGF-I on OPG message stability. Conditioned media from ST2 cells confirmed that IGF-I decreased secreted OPG, reducing levels by 42%, from 12.1-7 ng/ml at 48 h (P < 0.05). Similarly, IGF-I at 100 micro g/liter (13 nM) increased RANKL mRNA expression to 353 +/- 74% above untreated cells as assessed by real-time PCR. In vivo, low doses of rhGH when administered to elderly postmenopausal women only modestly raised serum IGF-I (to concentrations of 18-26 nM) and did not affect circulating OPG concentrations; however, administration of rhIGF-I (30 micro g/kg.d) for 1 yr to older women resulted in a significant increase in serum IGF-I (to concentrations of 39-45 nM) and a 20% reduction in serum OPG (P < 0.05). In summary, we conclude that IGF-I in a dose- and time-dependent manner regulates OPG and RANKL in vitro and in vivo. These data suggest IGF-I may act as a coupling factor in bone remodeling by activating both bone formation and bone resorption; the latter effect appears to be mediated through the OPG/RANKL system in bone.

Expression of the transcription factor GADD153 is an indicator of apoptosis for recombinant chinese hamster ovary (CHO) cells.

Loss of cell viability, through engagement of apoptotic cell death, represents a limitation to maintenance of high levels of productivity of recombinant animal cells in culture. The ability to monitor the status of recombinant cells, and to define indicators of their "well-being," would present a valuable approach to permit a rational intervention at appropriate times during culture. Growth arrest and DNA damage gene 153 (GADD153) is a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors and has been associated with apoptosis. We have examined the expression of GADD153 in conditions associated with apoptosis of recombinant CHO cells in batch culture. GADD153 expression is very low in CHO cells growing in the exponential phase of batch culture but is activated as cells enter the decline phase. Depletion of nutrients (glucose or glutamine) causes activation of GADD153 expression as does the imposition of endoplasmic reticulum stress. In all cases, there is a good relationship between the extent of apoptosis that occurs in response to each stress and the degree of GADD153 expression. In addition, nutrient refeeding or reversal of stress produces a concomitant decrease in expression of GADD153 and the susceptibility to apoptosis. Thus, GADD153 appears to offer a valid indicator of apoptosis and illustrates the potential for definition of monitors of cellular status related to the likelihood of apoptosis of cell populations.

A novel action of the newly described prolactin-releasing peptides: cardiovascular regulation.

The physiological relevance of the recently described prolactin-releasing peptides (PrRPs) has yet to be established. Here, we demonstrate the low potency of the PrRPs (minimum effective dose: 100 nM), compared to that observed for thyrotropin-releasing hormone (TRH, minimum effective dose: 1.0 nM), to stimulate prolactin (PRL) release from cultured pituitary cells harvested from lactating female rats. Anatomic studies question the role of these peptides in neuroendocrine control of lactotroph function. Instead, peptide and peptide receptor mapping studies suggest potential actions in hypothalamus and brainstem unrelated to the control of anterior pituitary hormone secretion. Intracerebroventricular (i.c.v. ) administration of both PrRP-20 and PrRP-31 (0.4 and 4.0 nmol) resulted in significantly increased mean arterial blood pressure in conscious, unrestrained rats [peak elevations vs. baseline: PrRP-20, 10% and 16%, low and high dose peptide; PrRP-31, 7% and 10%; compared to the response to 0.1 nmol angiotensin II (A II), 15-17%]. Similar doses of peptide did not significantly alter water drinking in response to overnight fluid deprivation, or thirst or salt appetite in response to an isotonic hypovolemic challenge. Thus, the effect on blood pressure appeared relatively specific. We suggest that these peptides, identified originally as ligands for a receptor found in abundance in pituitary gland, play a broader role in brain function and that the ability of them to stimulate PRL release may not represent their primary biologic function.

Transcriptional regulation of the expression of macrophage colony stimulating factor.

The regulatory regions for transcriptional control of the MCSF gene are unknown. We examined regulatory control in a 774-bp murine MCSF promoter transfected into MC3T3-E1 osteoblast-like and COS-7 cells. Deletion of upstream sequence from -635 increased basal activity of the promoter by at least four-fold, an increase that was maintained when PU.1, NFkappaB and Egr1/Sp1 consensus sequences were subsequently removed. Mutagenesis identified a suppressor element between -635 and -642 from the transcriptional start site and an oligonucleotide representing this sequence was retarded by nuclear cell protein. TNFalpha (1 ng/ml), PTH (5x10(-8) M), and IL-1alpha (100 pg/ml), which increased MCSF protein secretion, failed to enhance the transcriptional rate of the full-length promoter. TNFalpha was able to stimulate transcription of a heterologous reporter transfected into COS-7 containing multiple copies of the murine MCSF NFkappaB site inserted before a minimal promoter. In contrast, deletion of the same NFkappaB response element increased basal activity in the native promoter. Thus, the NFkappaB sequence may act as a negative regulator in the context of the endogenous promoter. Our results indicate that constitutive transcriptional activity conferred by the MCSF promoter may be damped by a suppressor protein. Transcriptional regulation, however, does not appear to be a major stimulatory mechanism for MCSF secretion.

Cardiovascular regulatory actions of the hypocretins in brain.

The hypocretins, also known as the orexins, are alternate translation products of a single gene. The recognition of their production in neurons of the rostral diencephalon, and their axonal localization in brain sites known to be important in the control of appetite, led to the demonstration of their orexogenic actions. However, these peptides are not as potent as other appetite stimulating neuropeptides and they have been localized in areas of brain more related to cardiovascular function. We verified the orexogenic actions of hypocretin-1 (Hcrt-1) and hypocretin-2 (Hcrt-2) in an ad libitum feeding model and identified the threshold dose to be 1 nmol when given into the lateral cerebroventricle (i.c. v.). Even at threshold doses for feeding, both Hcrt-1 and Hcrt-2 given i.c.v. into conscious, unrestrained rats stimulated significant elevations in mean arterial blood pressure, that appeared dose related. These elevations were relatively long lasting, mirroring the time course of a pressor dose of angiotensin II (0.1 nmol i.c.v.); however, the magnitude of blood pressure elevation to hypocretin did not equal that of A II. These data suggest an additional, non-appetitive action of the hypocretins and indicate that the peptide and receptor mapping studies may have predicted important roles for the peptides in the central nervous system control of cardiovascular function.

Role of NFkappaB in the regulation of macrophage colony stimulating factor by tumor necrosis factor-alpha in ST2 bone stromal cells.

Expression of MCSF in bone is important to the regulation of osteoclastogenesis. We show here that tumor necrosis factor-alpha (TNFalpha) increases the production of both soluble (sMCSF) and membrane-bound (mMCSF) macrophage colony stimulating factor by ST2 bone stromal cells. Treatment of ST2 cells with TNFalpha caused sMCSF levels to increase by 394+/-5% from basal; mMCSF rose by 316+/-66% from 30+/-10 per 100,000 cells in the same time. These increases were consistent with increased expression of mRNAs encoding both isoforms. Increases in MCSF mRNA are also seen after stimulation with dexamethasone. To investigate the potential role of NFkappaB in this TNFalpha effect, we treated cells with sodium salicylate (NaS), an inhibitor of NFkappaB translocation. NaS decreased TNFalpha-stimulated NFkappaB activation by 50% as assessed by EMSA. Despite inhibition of NFkappaB signaling, NaS enhanced TNFalpha-stimulated MCSF secretion and did not prevent TNFalpha-stimulated increases in sMCSF mRNA, suggesting that NFkappaB was not involved in TNFalpha effect on the gene. TNFalpha failed to stimulate transcription of a 774 nucleotide MCSF promoter-luciferase reporter transfected into ST2 cells which contained the NFkappaB consensus sequence. Deletion of the seven nucleotides containing the NFkappaB homology response sequence from the MCSF promoter increased basal gene transcription by twofold. TNFalpha thus contributes to an osteoclastogenic environment through upregulation of bone expression of both MCSF isoforms. Our data suggests that NFkappaB is not the major signaling pathway through which this occurs.

Antisense oligonucleotide treatment reveals a physiologically relevant role for adrenomedullin gene products in sodium intake.

Adrenomedullin (AM), a potent hypotensive peptide, is produced in numerous tissues including adrenal gland, kidney, brain and pituitary gland, where it acts to modify sodium homeostasis. Central AM administration dose-dependently inhibits sodium appetite. AM antisense oligonucleotide treatment significantly lowered peptide content in the hypothalamic paraventricular (PVN) nucleus and exaggerated the consumption of sodium. These results support a physiologic role for adrenomedullin gene products in the central regulation of sodium homeostasis.

Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats.

Peptides derived from postranslational processing of preproadrenomedullin exert potent hypotensive effects in the periphery. One of those peptides, adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats to inhibit water drinking and salt appetite and, in anesthetized rats, surprisingly to increase blood pressure. We examined the effects of AM and the other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP), on blood pressure in conscious rats. Both AM and PAMP elicited dose-related increases in mean arterial pressure after cerebroventricular administration. The hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral administration of phentolamine, indicating actions of the peptides in brain to stimulate sympathetic nervous system function. Blockade of central ANG II receptors with saralasin prevented the hypertensive effects of both ANG II and PAMP, suggesting recruitment of endogenous angiotensinergic systems by central PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at similar doses did nto significantly affect blood pressure. Furthermore, the hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior administration of the CGRP antagonist. We hypothesize that AM and PAMP exert cardioprotective effects in brain, which may counterbalance the volume-unloading actions of the peptides in the periphery.

Proadrenomedullin N-terminal 20 peptide inhibits adrenocorticotropin secretion from cultured pituitary cells, possibly via activation of a potassium channel.

Preproadrenomedullin is processed into at least two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Both peptides are hypotensive; however, they exert this action via differing mechanisms. In pituitary cells in culture, both basal and releasing factor-stimulated adrenocorticotropin (ACTH) secretion is inhibited by AM. Here we report that basal, but not stimulated, ACTH secretion from cultured rat pituitary cells is also inhibited by PAMP. The effect is dose-related, occurs in a physiologically relevant dose range that is similar to that of AM, and is blocked by the potassium channel blocker, glybenclamide. The failure of glybenclamide to inhibit AM's effects on ACTH secretion indicates that in pituitary, as in other tissues, these two products of the same prohormone can exert similar biologic activity, although via differing mechanisms.

Gender-biased activity of the novel prolactin releasing peptides: comparison with thyrotropin releasing hormone reveals only pharmacologic effects.

The prolactin- (PRL) releasing activities of the newly described PRL-releasing peptides (PrRPs) were compared to that of thyrotropin-releasing hormone (TRH) in dispersed, rat anterior pituitary cell cultures. A dose-related stimulation of PRL release by TRH was observed in cells harvested from both intact male and random cycle female pituitary donors. The minimum effective dose of TRH ranged from 1 to 10 nM. Neither PrRP-20 nor PrRP-31 significantly altered PRL secretion in cells from male donors even at doses as high as 1 microM. In cells harvested from females, only the highest doses of PrRP-20 and PrRP-31 tested (0.1 and 1.0 microM) significantly stimulated PRL secretion. The PRL-releasing action of TRH was observed already at 15 min of incubation, whereas those of PrRP-20 and PrRP-31 appeared only after 1 and 2 h of incubation, and the magnitude of PRL release in the presence of 1 microM PrRPs was significantly less than that of a similar dose of TRH. These data do not suggest a physiologically relevant role for the PrRPs in the neuroendocrine regulation of PRL secretion in intact male and nonlactating, random-cycle female rats.

Adrenomedullin inhibits salt appetite.

Adrenomedullin (AM) exerts profound natriuretic and vasodilatory effects in conscious animals. This newly discovered hormone also acts in the central nervous system to inhibit water drinking and in the pituitary gland to reduce basal and stimulated ACTH release. We investigated whether the natriuretic action of AM in kidney was matched by a central nervous system action to decrease salt intake. Isotonic hypovolemia induced in male rats by pretreatment with polyethylene glycol potently stimulates both water and salt water (0.3 mol/liter NaCl) drinking. Saline drinking was significantly inhibited when AM was administered into the lateral cerebroventricle before the drinking interval. The effect was dose related (dose range, 44-88 pmol), long lasting (> 5 h), and reversible (resolved at 24 h). When hypovolemic rats were administered antiserum to AM (intracerebroventricular administration) before the drinking interval, a significant 2-fold augmentation of saline drinking was observed. These data suggest that in addition to peripheral actions on cardiovascular and renal function and pituitary actions to inhibit ACTH release, AM may act within the central nervous system to determine fluid and electrolyte balance and, ultimately, blood pressure.

A 35 amino acid fragment of leptin inhibits feeding in the rat.

Peptide fragments of the larger 167 amino acid obesity gene related peptide (OBGRP), leptin, were tested for their ability to inhibit feeding in the rat. The C-terminal fragment, OBGRP 116-167 exerted only minimal inhibition of feeding when administered into the lateral cerebroventricle. No alteration in feeding was observed following administration of OBGRP 57-92. We hypothesized that the satiety effects of leptin reside in the N-terminal region of the peptide sequence. Significant, dose-related, and reversible inhibition of food intake was observed following central administration of the 35 amino acid fragment OBGRP 22-56. These results suggest that a small, readily synthesized fragment of the 167 amino acid peptide leptin may exert physiologically relevant satiety effects in brain revealing an endocrine feedback mechanism by which the adipocyte may modulate hypothalamic function.

The novel vasoactive hormone, adrenomedullin, inhibits water drinking in the rat.

The novel hormone, adrenomedullin (AdM), which exerts potent hypotensive effects in the periphery and natriuretic actions in the kidney, was found to be antidipsogenic. Cerebroventricular injection of AdM (22, 44, and 88 pmol) resulted in a dose-related diminution of water drinking in response to subsequent central administration of 100 pmol angiotensin II. Additionally, 88 pmol AdM significantly inhibited the drinking response to overnight water deprivation and hyperosmotic challenge. No significant effects of AdM in the doses tested were observed on blood pressure, heart rate, or motor activity. These results suggest that this novel hormone can act within the nervous system to complement its peripheral actions on fluid and electrolyte homeostasis, independent of a central action on cardiovascular function or locomotion.