Neuropeptide VF-associated satiety involves mu and kappa but not delta subtypes of opioid receptors in chicks

Neuropeptide VF (NPVF) induces satiety through hypothalamic interactions; however, the central mechanism that mediates these effects is poorly understood. Therefore, this study was conducted to explore some possible opioid receptor associated mechanisms of NPVF-induced satiety using chicks as models. Co-injection of NPVF and a mu opioid receptor antagonist (beta-funaltrexamine, FNA) did not have an additive suppressive effect on food intake compared to NPVF and FNA when injected alone. Contrary, co-injection of NPVF and a delta opioid receptor antagonist (ICI-174,864, ICI) caused a greater reduction in food intake than when both were injected alone. Co-injection of NPVF and a kappa opioid receptor antagonist (nor-binaltorphimine, BNI) did not cause an additive suppressive effect on food intake than when the two were injected alone. A reversal of neuropeptide Y and β-endorphin induction of food intake occurred when NPVF was co-injected. These results support that NPVF-induced satiety is mediated through mu and kappa but not delta subtypes of opioid receptors, and their ligands including neuropeptide Y and β-endorphin. Thus, NPVF-associated anorexia may be mediated via modulation of the chick's innate opioid-associated orexigenic system.     

Opioid μ-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Aim: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid μ‐receptors have been found in the MR, we studied the putative role of opioid μ‐receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. Methods: We measured pulmonary ventilation () and the body temperatures (Tb) of male Wistar rats before and after the selective opioid μ‐receptor antagonist CTAP (d ‐Phe‐Cys‐Tyr‐d ‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2, cyclic, 0.1 μg per 0.1 μL) was microinjected into the rMR during normoxia or after 60 min of hypoxia. Results: The animals treated with intra‐rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg^?1 min^?1) compared with the control group (790 ± 82 mL kg^?1 min^?1) (P < 0.05). No differences in the Tb were observed between groups during hypoxia. Conclusion: These data suggest that opioids acting on μ‐receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.     

mu- but not delta- and kappa-opioid receptor mediates the nucleus submedius interferon-alpha-evoked antinociception in the rat

Previous studies have indicated that interferon-alpha (IFN-alpha) can bind to opioid receptors and exerts an antinociceptive effect in both peripheral and central nervous systems. The current study investigated the antinociceptive effect of IFN-alpha unilaterally microinjected into the thalamic nucleus submedius (Sm) of rats on noxious thermal stimulus, and the roles of different subtypes of opioid receptors in mediating the Sm IFN-alpha-evoked antinociception. The results indicated that unilateral microinjection of IFN-alpha (4, 8, 16 pmol) into the Sm dose-dependently increased the hind paw withdrawal latency from the noxious heat stimulus, and this effect was reversed by pretreatment with non-selective opioid receptor antagonist naloxone (200 pmol) and specific mu-opioid receptor antagonist beta-FNA (1 nmol) into the same sites, whereas delta-opioid receptor antagonist ICI174,864 (1 nmol) and kappa-opioid receptor antagonist nor-BNI (1 nmol) failed to alter the effect of IFN-alpha. These results suggest that Sm is involved in IFN-alpha-evoked antinociception and mu- but not delta- and kappa-opioid receptor mediates the Sm IFN-alpha-evoked antinociception.     

B2 kinin receptors mediate the Indian red scorpion venom‐induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathway

Aim: This study was performed to delineate the kinin (receptor)‐dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom‐induced pulmonary oedema as well as the augmentation of cardio‐pulmonary reflexes evoked by phenyldiguanide (PDG). Methods: In urethane‐anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des‐ Arg, B₁ receptor antagonist; Hoe 140, B₂ receptor antagonist; N^ω‐nitro‐l ‐arginine methyl ester (l ‐NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K⁺_ATP channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom‐induced responses. Results: Intravenous injection of PDG (10 μg kg^?1) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 μg kg^?1) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom‐induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des‐Arg did not. l ‐NAME, methylene blue or glibenclamide also blocked the venom‐induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom. Conclusion: The results indicate that venom‐induced responses involve B₂ kinin receptors via the NO‐dependent guanylate cyclase‐cGMP pathway involving K⁺_ATP channels.     

Negative inotropic and chronotropic effects of δ-opioid receptor antagonists are mediated via non-opioid receptors

Ten-minute perfusion of intact isolated rat heart with Krebs-Henseleit solution containing δ-opioid receptor agonists (DPDPE, (−)-TAN-67) or δ-opioid receptor antagonists (naltrindole, TIPP[Ψ], ICI 174,864) at a final concentration of 0.1 mg/liter decreased HR, blood pressure in the left ventricle, and the rates of myocardial contraction and relaxation. Intravenous injection of δ-agonists (DPDPE, (−)-TAN-67, deltorphin II) or δ-antagonists (naltrindole, TIPP[Ψ], ICI 174,864) decreased HR in narcotized rats. Naloxone and naltrexone produced no effect on contractility and HR both in vivo and in vitro. Preliminary injection of naloxone and naltrexone did not prevent the negative chronotropic effect of ICI 174,864 in vitro. The negative inotropic and chronotropic effects of δ-opioid receptor antagonists are mediated by unknown non-opioid receptors in the heart. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 404–407, April, 2006     

Prevention of experimental epinephrine-induced arrhythmias with agonists of δ1- and δ2-opiate receptors

Agonists of δ₁- and δ₂-opiate receptors prevent epinephrine-induced arrhythmias in rats after intracerebroventricular administration. The antagonist of δ-opiate receptors ICI 174,864 blocks antiarrhythmic effect of the selective agonist of δ-opiate receptors DTLET and exhibits no antiarrhythmic activity by itself. It is shown that antiarrhythmic effect of DTLET is associated with increased vagal tone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 286–288, September, 1997     

B lymphocyte proliferation is suppressed by the opioid growth factor–opioid growth factor receptor axis: Implication for the treatment of autoimmune diseases

Endogenous opioids are known to repress the incidence and progression of autoimmune diseases. One native opioid peptide, [Met⁵]-enkephalin, termed the opioid gowth factor (OGF), interacts with the OGF receptor (OGFr) to suppress the expression of experimental autoimmune encephalomyelitis. The present study examined the role of the OGF-OGFr axis in the regulation of B lymphocyte proliferation. Murine B lymphocytes were stimulated with lipopolysaccharide. Both OGF and OGFr were present in all B lymphocytes. OGF had a dose-dependent effect on growth, with cell number inhibited by up to 43% at 72 h; no other synthetic or native opioid altered cell proliferation. Exogenous OGF depressed cell number in cultures treated with siRNAs for the classical opioid receptors, MOR (μ), DOR (δ), and KOR (κ), however this peptide had no effect in preparations exposed to siRNA for OGFr. The decrease in cell number by exogenous OGF was dependent on p16 or p21 cyclin-dependent inhibitory kinase pathways. Exposure to the opioid antagonist, naltrexone, did not change cell number from control levels. These results suggest that the OGF-OGFr axis is present and functional in B lymphocytes, but this system is not an autocrine regulator of cell proliferation. Thus, at least exogenous OGF and perhaps endogenous OGF by paracrine/endocrine sources, can be an immunosuppressant. Modulation of the OGF-OGFr axis may be a novel paradigm for the treatment of autoimmune diseases.     

Antinociceptive tolerance to the mu-opioid agonist DAMGO is dose-dependently reduced by MK-801 in rats

Morphine has been used in previous studies that investigate interactions between the spinal cord μ-opioid and N-methyl-d-aspartate (NMDA) receptors in mechanisms of antinociceptive tolerance. Although morphine acts primarily on the μ-receptor, it also activates other subtypes of opioid receptors. In the present study, the selective μ-opioid agonist, d-Ala²-N-Me-Phe⁴,Gly-ol⁵-enkephalin (DAMGO), was used to further test the hypothesis. Repeated intrathecal (i.t.) administration of 6 μg DAMGO (twice daily) in rats for 7 days resulted in an approximately 17-fold rightward shift of the cumulative dose–response curve (the tail-flick test) on Day 8 compared to that on Day 1. This rightward shift of the dose–response curve was prevented by the i.t. co-administration with DAMGO of the NMDA receptor antagonist MK-801 (10=5>2.5>>1.25 nmol>saline). Further, a lower dose range of MK-801 (2.5>1.25 nmol>0.625>0.313=saline) was effective to prevent the antinociceptive tolerance to a lower dose (1.5 μg) of DAMGO using the same i.t. administration regimen. Thus, the present results provide further evidence supporting a cellular and intracellular model of opioid tolerance involving interactions between the μ-opioid and the NMDA receptors in the spinal cord.     

The effect of angiotensin AT1 receptor blockade in the brain on the maintenance of blood pressure during haemorrhage in sheep

The effect of systemic or intracerebroventricular (ICV) infusion of the angiotensin AT₁ receptor antagonist losartan on blood pressure during hypotensive haemorrhage was investigated in five conscious sheep. Mean arterial pressure (MAP) was measured during haemorrhage (15 mL kg^?1 body wt). Losartan (1 or 0.33 mg h^?1) was given to sheep by ICV, intravenous or intracarotid administration, beginning 60 min before and continuing during the haemorrhage. During control infusion of ICV artificial cerebrospinal fluid, MAP was maintained until 13.16 ± 0.84 mL kg^?1 blood loss, when a rapid reduction of at least 15 mmHg in arterial pressure occurred (the decompensation phase). ICV infusion of losartan at 1 mg h^?1 caused an early onset of the decompensation phase after only 9.8 ± 0.8 mL kg^{? 1} of blood loss compared with control. Intravenous infusion of losartan (1 mg h^?1) also caused an early onset (P < 0.05) of the decompensation phase at 10.2 ± 1.0 mL kg^?1 blood loss. This dose of losartan inhibited the pressor response to ICV angiotensin II, but not to intravenously administered angiotensin II, indicating that only central AT₁ receptors were blocked. Bilateral carotid arterial administration of losartan at 0.33 mg h^?1 caused an early onset of the decompensation phase during haemorrhage at 11.06 ± 0.91 mL kg^?1 blood loss (P < 0.05), which did not occur when infused by intravenous or ICV routes. The results indicate that an angiotensin AT₁-receptor-mediated mechanism is involved in the maintenance of MAP during haemorrhage in sheep. The locus of this mechanism appears to be the brain.     

5-HT1A, but not 5-HT2 and 5-HT7, receptors in the nucleus raphe magnus modulate hypoxia-induced hyperpnoea

Aim: In the present study, we assessed the role of 5‐hydroxytryptamine (5‐HT) receptors (5‐HT_1A, 5‐HT₂ and 5‐HT₇) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia. Methods: To this end, pulmonary ventilation (V_E) and body temperature (T_b) of male Wistar rats were measured in conscious rats, before and after a 0.1 μL microinjection of WAY‐100635 (5‐HT_1A receptor antagonist, 3 μg 0.1μL^?1, 56 mm ), ketanserin (5‐HT₂ receptor antagonist, 2 μg 0.1μL^?1, 36 mm ) and SB269970 (5‐HT₇ receptor antagonist, 4 μg 0.1 μL^?1, 103 mm ) into the NRM, followed by 60 min of severe hypoxia exposure (7% O₂). Results: Intra‐NMR microinjection of vehicle (control rats) or 5‐HT antagonists did not affect V_E or T_b during normoxic conditions. Exposure of rats to 7% O₂ evoked a typical hypoxia‐induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY‐100635, SB269970 or ketanserin. The hypoxia‐induced hyperpnoea was not affected by SB269970 and ketanserin intra‐NMR. However, the treatment with WAY‐100635 intra‐NRM attenuated the hypoxia‐induced hyperpnoea. Conclusion: These data suggest that 5‐HT acting on 5‐HT_1A receptors in the NRM increases the hypoxic ventilatory response.     

Regulation of apical transporter of L‐DOPA in human intestinal Caco‐2 cells

The present study examined the nature of the apical inward L ‐3,4‐dihydroxyphenylalanine (L ‐DOPA) transporter in human intestinal epithelial Caco‐2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L ‐DOPA was promoted through an energy‐dependent and sodium‐insensitive transporter (K_m=33 μM ; V_max=2932 pmol/mg protein/6 min). This transporter was insensitive to N‐(methylamino)‐isobutyric acid, but competitively inhibited by 2‐aminobicyclo(2,2,1)‐heptane‐2‐carboxylic acid (BCH; IC₅₀=83 μM ). The organic cation inhibitor decynium 24 failed to affect the accumulation of L ‐DOPA, whereas the organic anion inhibitor 4,4′‐diisothiocynatostilbene‐2,2′‐disulphonic acid (DIDS) competitively inhibited L ‐DOPA uptake (IC₅₀=83 μM ). However, the apical‐to‐basal and basal‐to‐apical transepithelial transport and the cell accumulation of [³H]‐PAH was close to that of [¹⁴C]‐sorbitol and insensitive to DIDS (300 μM ). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H‐89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13‐dibutirate and chelerythrine) failed to affect the accumulation of L ‐DOPA. The Ca²⁺/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L ‐DOPA uptake (IC_50s of 53 and 252 μM , respectively), but the rise of intracellular Ca²⁺ by A23187 (1 μM ) and thapsigargin (1 μM ) played no role on L ‐DOPA uptake. It is concluded that Caco‐2 cells take up L ‐DOPA over the apical cell border through the sodium‐independent and pH‐sensitive L‐type amino acid transporter.     

Opiatergic mechanisms of cardioprotective and antiarrhythmic effects of adaptation

Adaptation to hypoxia and short-term immobilization stress, as well as preconditioning with Rhodiolae rosea extract produces pronounced antiarrhythmic and cardioprotective effects in the model of adrenergic damage to the heart. Preliminary blockade of opioid receptor significantly decreases the protective effect of adaptation. Using selective opiate receptor antagonists (naltrindole, ICI 174,864, and norbinaltorphimine) we show that the antiarrhythmic effect of adaptation is mediated predominantly via activation ofk-receptors, and to a lesser extent μ-and σ-receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 167–170, February, 1999     

Influence of opioid peptides on learning and memory processes in the chick

Several experiments were conducted to examine the effects of intracranial injection of opioid peptides and antagonists on learning and memory in the chick. Pretraining injection of [leu5]enkephalin and the selective delta receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) into the intermediate medial hyperstriatum ventrale (IMHV) produced impairment. ICI 174,864, a delta-selective antagonist, reversed the impairment produced by either [leu5]enkephalin or DPLE, results indicating that delta receptors may play a role in learning in the chick and suggesting that the impairment produced by [leu5]enkephalin is mediated through delta opioid receptors. beta-endorphin produced a naloxone-reversible impairment in performance, which suggests that this impairment is mediated by opioid receptors. Bilateral injection of beta-endorphin into the IMHV produced impairment, as did unilateral injection into the right, but not left, IMHV. Only bilateral injections into IMHV of [leu5]enkephalin were effective. These results suggest that the effects of beta-endorphin are centrally mediated whereas the effects of [leu5]enkephalin may be localized to other brain regions or are peripherally mediated. These initial results suggest that opioids are associated with learning and memory in the chick.     

The role of the adrenal medulla in cardiovascular responses to hypertonic saline in haemorrhaged conscious rats

The aim of this study was to determine if the adrenal medulla plays a role in mediating haemodynamic effects of hypertonic saline (HTS) resuscitation during haemorrhagic hypotension in conscious rats. Wistar-Kyoto rats were either adrenomedullectomized (ADMX, n = 11) or sham-operated (SHAM, n = 10) and implanted with intravascular catheters. Pre-haemorrhage resting mean arterial pressure (MAP) was lower in the ADMX than in the SHAM group. Haemorrhage was performed by withdrawal of blood through the venous catheter, and a MAP of 50 mmHg was maintained for 1 h by further withdrawal when necessary. Both groups responded to haemorrhage with marked bradycardia. Plasma adrenaline (A) rose 10-fold in response to hypotension in the SHAM group, while remaining at pre-haemorrhage levels in the ADMX group, indicating successful adrenal demedullation. Infusion of 2.0 ml kg^-1 HTS (NaCl 8.0 mg ml^-1 i.v.) produced an immediate increase in MAP and heart rate (HR) in both groups, to pre-haemorrhage values or higher. Plasma noradrenaline (NA) increased in both groups after HTS, while the high levels of A in the SHAM group slowly returned toward baseline. Plasma glucose and rate of haemodilution was higher in the SHAM group during and after hypotension. The maintenance of MAP above 60 mmHg was less effective in the SHAM group during the first 2 h after HTS, but after 24 h, pre-haemorrhage MAP was established in both groups. In conclusion, the adrenal medulla does not play a major role in the response to HTS resuscitation.     

Duration and mechanisms of the increased natural cytotoxicity seen after chronic voluntary exercise in rats

We have recently shown that in vivo natural cytotoxicity is enhanced after chronic exercise in spontaneously hypertensive rats (SHRs). In the present report, we have studied the duration of this augmentation and some possible mechanisms involved. Exercise consisted of voluntary running for 4–5 weeks, with the running distance ranging from 2.7–15.6 km day^?1 during the last week of running. In vivo cytotoxicity was measured as clearance of injected ⁵¹Cr-labelled YAC-1 lymphoma cells from the lungs. The in vivo natural cytotoxicity was increased in running SHRs, and also in SHRs that had their running wheel locked for 24 and 48 h prior to the experiment, and was still present after 96 h. The enhancement of in vivo cytotoxicity after 5 weeks of exercise was abolished after an acute injection of the β-adrenergic receptor antagonist timolol (0.5 mg kg^?1 i.v.), indicating that catecholamines are involved in this augmentation. Interestingly, 24 h after the last exercise bout, the increased natural cytotoxicity could be blocked by timolol. The opioid receptor antagonist naloxone given subcutaneously for 7 days by osmotic pumps (6 mg kg^?1 h^?1) could not reverse the increased in vivo cytotoxicity seen in the running SHRs, suggesting that opioid receptor mechanisms are not involved, or at least not the naloxone-sensitive μ-receptor. Natural immunity was not influenced by the histamine H₂ receptor antagonist ranitidine, either in controls or in runners, indicating that the natural killer cell-regulatory effect of histamine is not present in SHRs and does not seem to be involved in the exercise-induced changes in natural immune function. We conclude that the augmentation of in vivo natural cytotoxicity after voluntary chronic exercise in rats is long-lasting and that the augmentation is partly mediated by β-adrenergic receptors.     

Spinal cord long-term potentiation is attenuated by the NMDA-2B receptor antagonist Ro 25-6981

Aim: The NR2B‐containing N‐methyl‐d ‐aspartate (NMDA) receptors may be involved in a variety of phenomena including synaptic plasticity, memory formation and pain perception. Here we used the NMDA‐2B receptor antagonist Ro 25‐6981 to investigate the role of the NR2B‐containing NMDA receptors in spinal nociception. Methods: Extracellular single unit recordings were performed from dorsal horn wide dynamic range (WDR) neurones in intact urethane‐anaesthetized Sprague–Dawley rats. The responses of the WDR neurones evoked by C‐fibre activation after sciatic nerve stimulation were defined according to latencies. To block the dorsal horn NMDA‐2B receptors, the antagonist Ro 25‐6981 was applied topically onto the spinal cord. High‐frequency stimulation (HFS) of the sciatic nerve was used to induce spinal long‐term potentiation (LTP). Results: Spinal administration of the NMDA‐2B receptor antagonist Ro 25‐6981 had a clear antinociceptive effect at the spinal level (P < 0.05, C‐fibre evoked responses after 4 mm Ro 25‐6981 vs. C‐fibre evoked responses in baseline). Moreover, spinal administration of this antagonist clearly attenuated the magnitude of spinal cord LTP after HFS conditioning (P < 0.05, C‐fibre evoked responses after HFS vs. C‐fibre evoked responses after 8 mm Ro 25‐6981 + HFS). Conclusion: The present study indicates that expression of full LTP in dorsal horn neurones obtained by HFS conditioning may be dependent on the NMDA receptors containing the NR2B subunit. This suggests that activation of dorsal horn NR2B‐containing NMDA receptors may be involved in use‐dependent sensitization at the spinal level.     

Effect of angiotensin II and endothelin‐1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs

Aim: This study investigates angiotensin II and endothelin‐1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. Methods: Conscious dogs were pre‐treated with angiotensin II type 1 (AT₁) and/or endothelin‐A (ET_A) receptor blockers or not. Protocol 1: After a 60‐min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT₁ blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ET_A blockade with i.v. ABT‐627. Protocol 4: Likewise, but with combined AT₁plus ET_Ablockade. Results: In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1‐fold), endothelin‐1 (1.13‐fold), vasopressin (116‐fold), and adrenaline concentrations (3.2‐fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT₁ blockade, the MAP decrease was exaggerated (?40%) and glomerular filtration rate fell. During ET_A blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. Conclusions: Angiotensin II is more important than endothelin‐1 for the short‐term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin‐1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin‐1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage‐induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output – but not MAP – was similar in all protocols.     

Saccharide Polymers, 5

Summary: New “saccharide polymers” were synthesized via free radical polymerization. The saccharide compounds in copolymerisation reactions were 2,4,6‐tri‐O‐acetyl‐3‐deoxy‐D ‐erythro‐hex‐2‐enono‐1,5‐lactone ( 1 ), (Ac‐GEL 1 ) and 2,4,6‐tri‐O‐benzoyl‐3‐deoxy‐D ‐erythro‐hex‐2‐enono‐1,5‐lactone ( 2 ), (Bz‐GEL 2 ). These sugar monomers are easily obtained with high yield in a one step reaction from glucono‐δ‐lactone. They have a pyranoid structure containing an endocyclic double bond and they are electron acceptor compounds. Copolymerization reactions were carried out in solution and in substance. Copolymers with different sugar contents and low as well as high molecular weights were obtained. The structures and the compositions of the soluble saccharide polymers were established by elemental analysis, polarimetry, FTIR spectroscopy, ¹H and ¹³C NMR spectroscopy. Some characteristic properties, e.g., molecular weight, optical rotation and copolymerization parameters are reported.

Schematic conversion of glucono‐δ‐lactone to saccharide monomers.     

Peroxisome proliferator‐activated receptor‐β/δ modulates mast cell phenotype

The peroxisome proliferator‐activated receptor‐β/δ (PPARβ/δ) is known to have multiple anti‐inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone‐marrow‐derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ^+/+ mice expressed higher levels of high‐affinity IgE receptor (FcεRI) compared with Pparβ/δ^−/− mice. BMMCs from Pparβ/δ^+/+ mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ^−/− mice. Resting BMMCs from Pparβ/δ^+/+ mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal‐regulated kinases compared with Pparβ/δ^−/− mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype.     

Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium‐dependent vasodilation in the femoral artery of developing piglets

Mechanisms mediating endothelium‐dependent vasodilation were investigated in femoral artery rings from <2‐day‐old (newborn) and 2‐week‐old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)‐cyclic 3′,5′‐guanosine monophosphate (cGMP) and K⁺ channel‐activation to acetylcholine (ACh)‐induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K⁺ channel blockade and the intra‐arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS‐inhibitors N ^G‐monomethyl‐L ‐arginine acetate (L ‐NMMA; 100 μM ) or N^G‐nitro‐L ‐arginine (L ‐NOARG; 1–100 μM ), however, relaxation was significantly more reduced in femoral artery rings from 2‐week‐old than from newborn, with lower pD₂ values in the older age group. Inhibition of large (BK_Ca) conductance calcium‐sensitive K⁺ channels with tetraethylammonium chloride (TEA; 1 mM ), gave a significant rightward shift in the concentration‐response curves to ACh which was of the same magnitude in both age groups. The ACh‐induced vasodilation was abolished in both age groups by high K⁺ (20 mM ) in combination with L ‐NOARG (100 μM ). The relative increase in cGMP levels after addition of ACh (10 nM ) was significantly larger in rings from newborn compared with 2‐week‐old piglets (12‐ vs. four‐fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K⁺ channel blockade with TEA was the same in femoral artery rings from newborn to 2‐week‐old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.