Can adiponectin have an additional effect on the regulation of food intake by inducing gastric motor changes?

The regulation of food intake is a complex mechanism, and the hypothalamus is the main central structure implicated. In particular, the arcuate nucleus appears to be the most critical area in the integration of multiple peripheral signals.Among these signals, those originating from the white adipose tissue and the gastrointestinal tract are known to be involved in the regulation of food intake.The present paper focuses on adiponectin, an adipokine secreted by white adipose tissue, which is reported to have a role in the control of feeding by acting centrally. The recent observation that adiponectin is also able to influence gastric motility raises the question of whether this action represents an additional peripheral mechanism that concurs with the central effects of the hormone on food intake. This possibility, which represents an emerging aspect correlating the central and peripheral effects of adiponectin in the hunger-satiety cycle, is discussed in the present paper.     

Differential effects of the serotonin1A agonist, 8-OH-DPAT,on masculine and feminine sexual behavior of the ferret

Administration of the serotonin (5-HT)_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) facilitates the expression of masculine sexual behavior in male and female rats as well as in male rhesus monkeys and inhibits lordosis behavior in female rats. In the present study the effects of 8-OH-DPAT on masculine coital and feminine proceptive and receptive behaviors were evaluated in the ferret, a carnivore. Doses of 8-OH-DPAT (0.1 or 0.2 mg/kg) that facilitate masculine sexual behavior in rats inhibited masculine sexual behavior in castrated, estradiol benzoate (EB)-treated male ferrets. Lower doses of 8-OH-DPAT (5 or 10 µg/kg) had no effect on the expression of masculine sexual behavior in either males or females. In contrast to the female rat, administration of 8-OH-DPAT significantly facilitated receptive behaviors in ovariectomized, EB-treated female ferrets. None of the doses of 8-OH-DPAT tested modified proceptive behaviors of gonadectomized, EB-treated male or female ferrets, as assessed in a T-maze in which the subjects could choose to approach either a castrated, sexually inactive male or a castrated, testosterone-primed stud male. Thus whereas the 5-HT_1A receptor agonist 8-OH-DPAT facilitates masculine sexual behavior and inhibits lordosis in the rat, it inhibits masculine sexual behavior and facilitates receptivity in the ferret. The different effects of 8-OH-DPAT observed in these two species may reflect differences in the neural control of their masculine coital and feminine receptive responses, respectively.     

Adiponectin affects the mechanical responses in strips from the mouse gastric fundus

AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P 0.05). The effects of ADPN were no longer observed in the presence of the nitric oxide(NO) synthesis inhibitor L-NG-nitro arginine(L-NNA)(P 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.     

The G protein‐coupled oestrogen receptor,GPER1, mediates direct anti‐inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert

It has been well established, particularly in animal models, that oestrogens exert neuroprotective effects in brain areas linked to cognitive processes. A key protective role could reside in the capacity of oestrogen to modulate the inflammatory response. However, the direct neuroprotective actions of oestrogens on neurones are complex and remain to be fully clarified. In the present study, we took advantage of a previously characterised primary culture of human cholinergic neurones (hfNBM) from the foetal nucleus basalis of Meynert, which is known to regulate hippocampal and neocortical learning and memory circuits, aiming to investigate the direct effects of oestrogens under inflammatory conditions. Exposure of cells to tumour necrosis factor (TNF)α (10 ng mL^‐1) determined the activation of an inflammatory response, as demonstrated by nuclear factor‐kappa B p65 nuclear translocation and cyclooxygenase‐2 mRNA expression. These effects were inhibited by treatment with either 17β‐oestradiol (E₂) (10 nmol L^‐1) or G1 (100 nmol L^‐1), the selective agonist of the G protein‐coupled oestrogen receptor (GPER1). Interestingly, the GPER1 antagonist G15 abolished the effects of E₂ in TNFα‐treated cells, whereas the ERα/ERβ inhibitor tamoxifen did not. Electrophysiological measurements in hfNBMs revealed a depolarising effect caused by E₂ that was specifically blocked by tamoxifen and not by G15. Conversely, G1 specifically hyperpolarised the cell membrane and also increased both inward and outward currents elicited by a depolarising stimulus, suggesting a modulatory action on hfNBM excitability by GPER1 activation. Interestingly, pretreating cells with TNFα completely blocked the effects of G1 on membrane properties and also significantly reduced GPER1 mRNA expression. In addition, we found a peculiar subcellular localisation of GPER1 to focal adhesion sites that implicates new possible mechanisms of action of GPER1 in the neuronal perception of mechanical stimuli. The results obtained in the present study indicate a modulatory functional role of GPER1 with respect to mediating the oestrogen neuroprotective effect against inflammation in brain cholinergic neurones and, accordingly, may help to identify protective strategies for preventing cognitive impairments.     

Relaxin influences ileal muscular activity through a dual signaling pathway in mice

AIM To investigate the signaling pathways involved in the relaxin(RLX) effects on ileal preparations from mice through mechanical and electrophysiological experiments.METHODS For mechanical experiments, ileal preparations from female mice were mounted in organ baths containing Krebs-Henseleit solution. The mechanical activity was recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrophysiological measurements were performed in current-and voltage-clamp conditions by a microelectrode inserted in a single smooth muscle cell(SMC) of the ileal longitudinal layer. Both the membrane passive properties and inward voltage-dependent L-type Ca2+ currents were recorded using suitable solutions and voltage stimulation protocols.RESULTS Mechanical experiments showed that RLX induced a decay of the basal tension and a reduction in amplitude of the spontaneous contractions. The effects of RLX were partially reduced by 1 H-[1,2,4]oxadiazolo[4,3-a ]-quinoxalin-1-one(ODQ) or 9-cyclopentyladenine mesylate(9 CPA), inhibitors of guanylate cyclase(GC) and adenylate cyclase(AC), respectively, and were abolished in the concomitant presence of both drugs. Electrophysiological experiments demonstrated that RLX directly influenced the biophysical properties of ileal SMCs, decreasing the membrane conductance, hyperpolarizing the resting membrane potential, reducing the L-type calcium current amplitude and affecting its kinetics. The voltage dependence of the current activation and inactivation time constant was significantly speeded by RLX. Each electrophysiological effect of RLX was reduced by ODQ or 9 CPA, and abolished in the concomitant presence of both drugs as observed in mechanical experiments. CONCLUSION Our new findings demonstrate that RLX influences ileal muscle through a dual mechanism involving both GC and AC.