Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 271 records · Page 15Linked to original sources

PubMed1996

Hypothalamic paraventricular nucleus involvement in the pressor response to N-methyl-d-aspartic acid in the periaqueductal grey matter.

The aim of this study was to demonstrate paraventricular hypothalamic nucleus (PVN) involvement in the cardiovascular changes induced by N-methyl-d-aspartic acid (NMDA) microinjections at the level of periaqueductal grey (PAG) matter. The study was carried out in anaesthetized rats and the arterial blood pressure monitored by a polygraph. NMDA injections (0.68-6.8 nmol/rat) into the PAG area induced a significant increase in blood pressure. After pretreatment by injection of the NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (2-APV, 0.05-5 nmol/rat) into the PVN, administration of NMDA (0.68 nmol/rat) into the PAG area elicited a decrease, rather than an increase, of blood pressure. We observed a significant reduction of the pressor effect induced by 6.8 nmol/rat NMDA after 2-APV injection into the PVN. 2-APV injection into the dorsomedial hypothalamic nucleus, an area near the PVN, did not modify the increase in blood pressure induced by NMDA in the PAG area. We suggest the existence of a glutamatergic connection between the PAG area and the PVN in the cardiovascular effects of NMDA.

Animals↗

PubMed1996

Biosynthesis in vitro of neolactotetraosylceramide by a galactosyltransferase from mouse T-lymphoma: purification and kinetic studies; synthesis of neolacto and polylactosamine core.

The galactosyltransferase, GalT-4, which catalyses the biosynthesis in vitro of neolactotetraosylceramide, nLcOse4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) from lactotriaosylceramide, LcOse3Cer (Glc NAc beta 1-3Gal beta 1-4Glc-Cer), and UDP-galactose has been purified 107 500-fold from a mineral oil induced mouse T-lyphoma P-1798, using affinity columns. The purified enzyme is partially stabilized in the presence of phospholipid liposomes. Two closely migrating protein bands of apparent molecular weights 56 kDa and 63 kDa were observed after sodium dodecyl sulfate polyacrylamide gel electrophoresis of highly purified mouse GalT-4. These two protein bands, when subjected to limited proteolysis, resulted in three peptides with identical mobilities indicating amino acid sequence identity between the proteins. Both protein bands from P-1798 gave a positive immunostain when tested with polyclonal antibody against bovine lactose synthetase (UDP-Gal:Glc beta 4-galactosyltransferase) following Western blot analysis on nitrocellulose paper. The enzyme has a pH optimum between 6.5 and 7.0 and like all other galactosyltransferases, GalT-4 has absolute requirements for divalent cation (Mn2+). The K(m) values for the substrate LcOse3Cer and donor UDP-galactose are 110 and 250 microM, respectively. Substrate competition studies with LcOse3Cer and either asialo-agalacto-alpha 1-acid glycoprotein or N-acetylglucosamine revealed that these reactions might be catalysed by the same protein. The only other glycolipid which showed acceptor activity toward the purified GalT-4 was iLcOse5Cer (GlcNAc beta 1-1-3Gal beta 1-4Lc3), the precursor for polylactosamine antigens. However, competition studies with these two active substrates using the most purified enzyme fraction, revealed that these two reactions might be catalysed by two different proteins since the experimental values were closer to the theoretical values calculated for two enzymes. Interestingly however, it seems that the GalT-4 from P-1798 has an absolute requirement for an N-acetylglucosamine residue in the substrate since the lyso-derivative (GlcNH2 beta 1-3Gal beta 1-4Glc-sphingosine) of the acceptor glycolipid LcOse3Cer is completely inactive as substrate while the K(m) and Vmax of the reacetylated substrate (GlcNAc beta 1-3Gal beta 1-4Glc-acetylsphingosine) was comparable with LcOse3Cer. Autoradiography of the radioactive product formed by purified P-1798 GalT-4 confirmed the presence of nLcOse4Cer, as the product cochromatographed with authentic glycolipid. The monoclonal antibody IB-2, specific for nLcOse4Cer, also produced a positive immunostained band on TLC as well as giving a positive ELISA when tested with radioactive product obtained using a highly purified enzyme from mouse P-1798 T-lymphoma.

Animals↗

PubMed1996

Selective and non-selective ET antagonists reveal an ETB receptors mediated ET-1-induced behavioural effect in conscious rats.

The injection of endothelin-1 (ET-1) (1 pmol/rat) into the dorsolateral periaqueductal gray (PAG) area of freely moving rats induced rotation along the long axis of the body (barrel-rolling). Preinjection (10 min before) of BQ-788 (an ETB receptor selective antagonist; 5 nmol) or bosentan (an ETA/ETB receptor non-selective antagonist; 10 nmol) to the PAG reduced the behavioral response to ET-1. In contrast, pretreatment with FR139317 (an ETA receptor selective antagonist; 5 nmol) did not affect the ET-1-induced barrel-rolling. These results suggest that barrel-rolling induced by microinjection of ET-1 into the PAG area is predominantly mediated via ETB-like receptors.

Animals↗

PubMed1996

Effects of in vitro 5-HT1 receptor activation in guinea pig trachea.

5-hydroxytryptamine (5-HT) has been reported to show some effects in respiratory tissues by activation of different subtype receptors. It has been demonstrated that 5-HT2 receptor activation causes in vivo and in vitro airways contraction and enhances effects of cholinergic nerve-mediated responses, whereas 5-HT1 receptor activation seems to be related to a relaxant effect. Moreover, in isolated guinea pig ascendens colon preparations 5-HT1 activation causes relaxation by involvement of nitric oxide (NO). The aim of this study was to investigate the effects of 5-HT1 receptor activation in guinea pig trachea as well as NO probable role in this activation. In tissues pretreated with both ketanserin (10 microM), an antagonist of 5-HT2 receptors, and ondansetron (10 microM), an antagonist of 5-HT3 receptors, 5-HT (from 10 nM to 10 mM) relaxed guinea pig trachea precontracted with acetylcholine (ACh, 100 microM). Carboxamidotryptamine (5-CT, from 10 nM to 10 mM), an agonist of 5-HT1 receptors, as well relaxed guinea pig trachea precontracted with ACh (100 microM). A pretreatment with NAN-190 (from 10 nM to 100 microM), a 5-HT1A selective antagonist, reduced the 5-HT and 5-CT relaxant effects but only at very high concentrations. Finally, a pretreatment with L-nitro-arginine-methyl-ester (L-NAME, 1 mM), an inhibitor of NO-synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, did not modify 5-HT and 5-CT responses in guinea pig trachea. In conclusion, this study suggests a 5-HT relaxant activity in guinea pig trachea via a 5-HT1 receptor activation without any NO pathway involvement. However, further investigations are needed to clarify which 5-HT1 receptor subtype is involved in 5-HT relaxant effect.

Acetylcholine↗

PubMed1996

Involvement of nitric oxide in cardiorespiratory regulation in the nucleus tractus solitarii.

The aim of this study was to investigate whether nitric oxide (NO) is involved in cardiorespiratory regulation in the nucleus tractus solitarii (NTS). Unilateral microinjections (50 nl) of the NO-donor, sodium nitroprusside (SNP, 40-100-200 mM), into the NTS of anaesthetized rats elicited dose-dependent apnea (7.3 +/- 2.3 sec; 28.6 +/- 5.7 sec; 35.6 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (8.4 +/- 3.1 mmHg; 18.2 +/- 5.8 mmHg; 25.8 +/- 6.7 mmHg, respectively; n = 6). Similarly, unilateral micro-injections (50 nl) of another NO-donor, 3-morpholinosydnonimine (SIN-1, 20-40-100 mM), also induced apnea (5.1 +/- 2.4 sec; 8.7 +/- 4.3 sec; 26.3 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (6.2 +/- 2.3 mmHg; 11.1 +/- 3.3 mmHg; 18.3 +/- 6.1 mmHg, respectively; n = 6). The SNP- and SIN-1-induced apnea and arterial blood pressure decrease were significantly (p < 0.01) blocked by a 3 min pretreatment with two calcium-channel blockers, diltiazem (0.1 mM) and cobalt (10 mM), while lower doses (diltiazem 0.01 and cobalt 1) were ineffective. Microinjections of diltiazem (0.01 mM) and cobalt (1 mM) alone did not induce any change in basal cardiorespiratory values like diltiazem (0.1 mM) and cobalt (10 mM). These data suggest that NO may be involved in NTS cardiorespiratory regulation via calcium-channel activation.

Animals↗

PubMed1996

Structural features of U6 snRNA and dynamic interactions with other spliceosomal components leading to pre-mRNA splicing.

In the spliceosome, the pre-mRNA, U2 and U6 snRNAs fold into a catalytic structure exhibiting striking similarities with domain V and VI of group II introns. Building of this tripartite structure implies that an evolutionary conserved base pairing between U4 and U6 snRNAs should be disrupted to allow potentially U6 catalytic residue to interact with U2 snRNAs and the pre-mRNA. The steps leading to U4/U6 disruption have been recently discovered and have been shown to involve a modification of the 3' end of U6 snRNA and the hnRNP C protein.

Base Composition↗

PubMed1996

Automatic external defibrillators in the hospital as well?

When a cardiac arrest occurs in a non-intensive area of the hospital, the emergency response is not always adequate from the point of view of timeliness and technical quality. The aims of this study were evaluate an experimental programme to improve the CPR skills of staff operating in non-intensive areas of our general hospital and to test the usefulness of placing automatic external defibrillators (AEDs) within these areas. In the experimental phase, two AEDs were placed in 2 non-intensive wards of our hospital for 8 months. The staff of these wards received specific training in CPR and early defibrillation (CPR-D). The devices were used in 19 cases; for defibrillation in four cases of ventricular fibrillation (VF) (three patients were discharged alive from hospital), and for monitoring three supraventricular arrhythmias, one bradyarrhythmia and 11 cardiac rhythms during critical situations. In the implementation phase, four AEDs were indefinitely assigned to as many non-intensive awards. Periodical CPR-D courses and refresher exercises were run; the cardiology staff co-operated in the maintenance of the AEDs and in the registration of technical and clinical data. In the first period of this phase (9 months), AEDs were utilized in 24 cases by the ward-staff: in nine cases for VF (three patients were discharged alive from hospital) and in 15 cases for other rhythm detection in critical conditions. The number and the quality of these uses seem to confirm the favourable impact of the adoption of a more user-friendly defibrillator, such as an AED. The active co-operation between intensive and non-intensive staff was important to facilitate a quick activation of the chain of survival outside the intensive care units. We conclude that AEDs, which were developed for out-of-hospital use by non-physician operators, are suitable for use inside the hospital as well.

Adult↗

PubMed1996

Angiotensin II, via an action at AT1 receptors, may modulate the behavioural effects of ET-1 in conscious rats.

The injection of endothelin-1 (ET-1) (1 pmol/rat) into the dorsolateral periaqueductal gray (PAG) area of freely moving rats induced rotation along the long axis of the body (barrel-rolling). Preinjection (10 min before) of losartan (a selective AT1 receptor antagonist; 50 nmol) to the PAG area reduced the behavioural response to ET-1. In contrast, pretreatment with PD123319 (a selective AT2 receptor antagonist; 50 nmol) did not affect the ET-1-induced barrel-rolling. These results indicate that endogenous angiotensin II, via an action on AT1 receptors, contributes to the barrel-rolling of ET-1 within the brain.

Angiotensin I↗

PubMed1996

Increase of B-50/GAP-43 immunoreactivity in uninjured muscle nerves of MDX mice.

Lack of dystrophin in mdx mice leads to muscle fibre degeneration followed by the formation of new myofibres. This degeneration-regeneration event occurs in clusters. It is accompanied by inflammation and remodelling of the intramuscular terminal nerve fibres. Since the growth-associated protein B-50/GAP-43 has been shown to be involved in axonal outgrowth and synaptic remodelling following neuronal injury, we have investigated the presence of B-50 in gastrocnemius and quadriceps muscles of mdx mice. Using immunocytochemistry we demonstrate increased presence of B-50 in terminal nerve branches at motor endplates of mdx mice, particularly in the clusters of de- and regenerating myofibres. In comparison, the control mice displayed no B-50 immunoreactivity in nerve fibres contacting motor endplates. Our findings indicate that during axonal remodelling and collateral sprouting the B-50 level in the terminal axon arbours is increased although there is no direct injury to the motoneurons. We suggest that the degenerating target and/or the inflammatory reaction induces the increased B-50 level in the motoaxons. The increased B-50 may be important for sprouting of the nerve fibres and re-establishment of synaptic contacts, and in addition, for maturation and survival of the newly formed myofibres.

Acetylcholinesterase↗

PubMed1996

A multinational economic evaluation of rhDNase in the treatment of cystic fibrosis.

Economic evaluations of pharmaceuticals are increasingly being conducted in conjunction with randomized phase III clinical trials to meet the demand for pharmacoeconomic data when new products are launched. While the need for such data is often global, the trials in which relevant information may be collected are often conducted in only one or a limited number of countries. A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others. We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease (rhDNase), which is used to improve pulmonary function in patients with cystic fibrosis (CF). The objective of these evaluations was to estimate the potential impact of rhDNase therapy in France, Germany, Italy, and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections (RTIs) in patients with CF. Analyses of economic impact were undertaken both with and without adjustment for differences in practice patterns between the United States and the countries of interest. Our findings suggest that rhDNase therapy may reduce the cost of RTI-related care by between US$600 and US$1,100 over a 24-week period; the cost of rhDNase is not included in these figures, as a price was unavailable when our analyses were undertaken. Despite methodologic challenges, economic evaluations that meet the information needs of decision makers in diverse countries can nonetheless be undertaken in conjunction with phase III clinical trials.

Clinical Trials, Phase III as Topic↗

PubMed1996

Re-introduction of referents in Italian children's narratives.

In this study we investigate the re-introduction of referents in the Frog stories told by Italian children aged 4-10 (N = 100). We found that for every age group full nouns are the most frequent forms used for reference re-introduction. Null forms, such as clitic pronouns or person/number inflection on the verb, are the second most frequent forms. A detailed analysis of null forms shows that children of different ages exploit different properties of the verbal and non-verbal context which can make a referent predictable. Compared to preschoolers, elementary school children are more likely to use null forms when the semantic content of the verb, or the structure of the preceding text make referents inferrable. On the other hand, preschoolers tend to exploit the importance of a character in the story plot, or the visual availability of the referent in the non-verbal context, as properties that make an entity salient enough to prevent the speaker from using overt linguistic forms such as full nouns. Our study confirms results of previous research, showing that elementary school children are more competent than preschoolers in integrating the semantic content of the current utterance into the context generated by previous discourse.

Age Factors↗

PubMed1996

Pain pressure threshold in cluster headache patients.

Pain perception threshold (PPT) in the head was assessed with a pressure algometer in 58 cluster headache (CH) patients (52M, 6F; 41 episodic and 17 chronic). Fourteen patients in cluster period were retested in remission. Thresholds were assessed at 10 symmetrical points on each side of the head and at the deltoid. Compared with controls (n = 50), CH patients had lower PPT in the head and in the deltoid. PPT was lower on the symptomatic side than on the non-symptomatic side in patients with episodic CH during a cluster period (p < 0.001) and in patients with chronic CH (p < 0.05). This pattern was more evident during a cluster period than during remission (p < 0.05). A reduced PPT did not correlate with illness duration and pain side. The lowest PPT mean values were found at the anterior and intermediate levels of the temporal muscle on the symptomatic side. These results imply a central mechanism underlying the pathogenesis of CH.

Adult↗

PubMed1996

Distribution of endothelin-1-receptor subtypes in rat portal vein.

Endothelin-1 (ET-1), a potent vasoactive peptide, was first isolated from cultured porcine endothelial cells. Subsequent studies revealed the existence of two additional related peptides, ET-2 and ET-3, and at least two distinct ET-receptor subtypes, ETA (selective for ET-1) and ETB (nonselective for ET isopeptides). These isopeptides and receptors are widely distributed in many tissues and are involved in numerous biological responses. The aim of this study was to identify the eventual distribution of the two distinct endothelin-receptor subtypes in isolated endothelium-denuded rat portal vein rings (PVRs) and strips (PVSs). BQ-123 (0.6, 1, and 6 microM) and PD-145065 (0.06, 0.1, 0.6, and 6 microM) were used to differentiate the subtypes because they are selective antagonists for ETA and nonselective antagonists for ETA-ETB receptors, respectively. To characterize the ET receptors further, sarafotoxin-S6c (a selective ETB-receptor agonist) and IRL-1038 (a selective ETB-receptor antagonist) were used. In PVRs, cumulative additions of ET-1 (0.1-100 nM) caused graded and slow contractions and potentiated spontaneous rhythmic contractions. The EC50 values and maximal response to 100 nM of ET-1 were 2.72 nM and 0.75 g, respectively (n = 7). PVSs showed ET-1 EC50 values very similar to those of PVRs, but Emax values to 100 nM of ET-1 were significantly lower (Emax = 0.33 g; n = 7). Moreover, ET-1 clearly increased the amplitude and frequency of spontaneous contractions in both types of specimens, although these were greater in the PVSs. Thirty-minute incubation with the selective ETA-receptor antagonist BQ-123 blunted ET-1-induced effects in PVS specimens but only weakly antagonized ET-1-induced contractions in PVRs. In contrast, the nonselective ETA-ETB-receptor antagonist PD-145065 significantly shifted the ET-1 concentration-response curve to the right in PVRs and partially inhibited ET-1 effects in PVSs. Moreover, sarafotoxin-S6c (0.1-100 nM) contracted PVRs and PVSs in a similar manner to ET-1; its effects were antagonized by IRL-1038 only at the PVR level. The differences observed in PVR and PVS specimens in response to agonists and antagonists of ET confirmed the great heterogeneity of endothelin-sarafotoxin receptors. In our experimental models, functionally ETB-like (or non-ETA) receptors seem mostly to mediate vasoconstriction.

Animals↗

PubMed1996

Neuronal precursors in the postnatal mouse cerebellum are fully committed cells: evidence from heterochronic transplantations.

Neural progenitors are thought to be multipotent cells whose adult phenotype is determined by extrinsic influences acting during and immediately after their last mitosis. To test this hypothesis, postnatal cerebellar precursor cells were placed in the heterochronic cellular environment of the embryonic mouse cerebellar anlage and the resulting phenotypes were determined. To identify the cells arising from postnatal precursors, tissue fragments taken from 3- to 8-day-old cerebellum of several transgenic mouse lines (each expressing the lacZ reporter gene in different sets of neuronal populations) were mixed with fragments taken from the wild-type cerebellar primordium of 12- or 13-day-old embryos. The fragments were dissociated and grafted into the cerebellum of adult mice. The phenotype acquired by postnatal precursors in the mixed grafts was determined by their morphology and ultrastructural features and by the expression of specific markers. Only two adult phenotypes were generated by these precursors: granule cells and molecular layer interneurons. Most granule cells were well integrated in the trilaminated cortex of the graft, being positioned in their proper layer both during development and after complete maturation. By contrast, basket and stellate cells were always ectopic, remaining outside the molecular layer. These results indicate that at least two distinct progenitor cells are present in the postnatal cerebellar cortex under the experimental conditions of this study. Both progenitors appear to be strictly specified at the time of grafting, and neither their identify nor the expression of their major distinctive features are significantly influenced by local signals emerging from the cellular environment of the embryonic cerebellar anlage.

Aging↗

PubMed1996

Topographically organized climbing fibre sprouting in the adult rat cerebellum.

Adaptive recovery following brain injury requires the topography of projection maps to be restored. In the adult mammalian brain, the regeneration of severed axons does not normally occur and repair mainly relies on collateral reinnervation from uninjured neurons. Although reinnervation can be target specific at the single cell level, it is not known if the new connections are organized correctly. The normal olivocerebellar projection had precise topography in which subnuclei of the inferior olive terminate as climbing fibres on chemically defined bands of cerebellar Purkinje cells. This precision has been exploited to determine the topography of climbing fibre sprouting following an inferior olive lesion in the adult rat. Collateral reinnervation was found to respect the boundaries between the Purkinje cell compartments. Thus, topographical cues are available in the adult during post-lesion plasticity to guide the restoration of the olivocerebellar projection map.

Animals↗

PubMed1996

Effects of S-ethylisothiourea, a potent inhibitor of nitric oxide synthase, alone or in combination with a nitric oxide donor in splanchnic artery occlusion shock.

1. The aim of this study was to compare the effects of an intravenous infusion of a potent and non selective nitric oxide synthase inhibitor S-ethylisothiourea (Ethyl-TU) with that of a nitric oxide (NO) donor on the pathological sequelae associated with splanchnic artery occlusion (SAO) shock. In addition the effects of the combination of these two treatments were also investigated. 2. SAO shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham operated animals were used as controls. Survival time, white blood cell (WBC) count, mean arterial blood pressure, myeloperoxidase activity (MPO; studied as a quantitative means to evaluate neutrophil accumulation) and the responsiveness of aortic rings to acetylcholine (ACh, 10 nM-10 microM) and to phenylephrine (PE, 1 nM-10 microM) were studied. 3. SAO shocked rats had a decreased survival rate (0% survival 2 h after the release of occlusion) and survival time (76 +/- 10 min), increased MPO activity in the ileum (3.39 +/- 0.8 u x 10(-3) g-1 tissue), a marked leukopenia and a profound hypotension. In addition aortic rings from shocked rats showed a marked hyporeactivity to PE and reduced responsiveness to ACh. Endothelium denuded aortic rings had also a marked hyporeactivity to PE. 4. In vivo administration of Ethyl-TU (0.1 mg kg-1 h-1, beginning 1 min after the onset of reperfusion) significantly increased survival time and rate, improved mean arterial blood pressure, restored the responsiveness to PE, but did not change MPO activity, leukopenia or the impairment in the responsiveness of aortic rings to ACh. Addition of Ethyl-TU (2 microM) to endothelium denuded aortic rings in vitro, restored the marked hyporeactivity to PE. Administration of the NO donor C87-3754 (0.75 mg kg-1 h-1, beginning 1 min after the onset of reperfusion) slightly increased survival time and reduced MPO activity and leukopenia, but did not change survival rate and mean arterial blood pressure. In addition C87-3754 restored the responsiveness of aortic rings to ACh to control values, but did not modify the hyporeactivity to PE. The combination of these two interventions produced a higher degree of protection than either Ethyl-TU or C87-3754 alone. In fact, co-administration of Ethyl-TU plus C87-3754 completely prevented mortality, reduced MPO activity, attenuated leukopenia and the profound hypotension and restored the impaired responsiveness of aortic rings to PE and ACh. 5. Our study suggests that treatment with a nitric oxide synthase inhibitor combined with an NO donor may be a new therapeutic approach to the treatment of splanchnic artery occlusion shock.

Acetylcholine↗

PubMed1996

M1 and M3 muscarinic receptors in human pulmonary arteries.

1. Acetylcholine (ACh) and the M1 agonists (McN-A-343 or PD142505) relaxed human isolated pulmonary arteries which were pre-contracted with noradrenaline (10 microM). In preparations where the endothelium had been removed ACh induced a contractile response whereas the M1 agonists (McN-A-343 or PD142505) had no effect. 2. ACh- and McN-A-343-induced relaxations were abolished after treatment of endothelium-intact preparations with the drug combination NG-nitro-L-arginine (L-NOARG: 0.1 mM) and indomethacin (1.7 microM). 3. The affinity (pKB value) for pirenzepine was higher in human pulmonary arteries when tissues were relaxed with McN-A-343 as compared with ACh (pKB values, 7.71 +/- 0.30 (n = 4) and 6.68 +/- 0.15 (n = 8), respectively). In addition, the affinity for pFHHSiD against McN-A-343- and ACh-induced relaxations was 6.86 +/- 0.13 (n = 3) and 7.35 +/- 0.11 (n = 9) respectively. 4. The low affinities for methoctramine in human isolated pulmonary arteries with the endothelium either intact or removed, suggested the lack of involvement of M2 and M4 receptors in the Ach responses. 5. Phenoxybenzamine (3 microM: 30 min) abolished both ACh contraction and relaxation in human pulmonary artery. The ACh contraction was present when the phenoxybenzamine treatment was preceded by incubation with pFHHSiD (2 microM) but not with pirenzepine (1 microM). In addition, the ACh relaxation was present when preparations were treated with either pFHHSiD (2 microM) or pirenzepine (1 microM), before exposure to phenoxybenzamine. 6. These results in human isolated pulmonary arteries support the notion that only M3 receptors, on smooth muscle, mediate the ACh-induced contraction whereas M3 and M1 receptors are involved in the endothelium-dependent ACh-induced relaxation.

Acetylcholine↗

PubMed1996

Synthesis and SAR study of imidazo[2,1-b]benzothiazole acids and some related compounds with anti-inflammatory and analgesic activities.

Some (un)substituted imidazo[2,1-b]benzothiazole carboxylic or acetic acids and some related compounds, i.e. imidazo[2,1-b]naphthol[2,1-d]thiazole, 4H-imidazo[2,1-c][1,4]benzothiazine, 4,5-dihydroimidazo[2,1-d][1,5]benzothiazepine carboxylic and acetic acids were synthesized and tested in vivo in order to study the structure-activity relationships (SAR) of their antiinflammatory and analgesic activities. Pharmacological assays confirmed the interest of this class of compounds as potential antiinflammatory and analgesic drugs with low side effects.

Acetates↗