Biomedical subjects

R G Andersson

Publications and source records attributed to R G Andersson.

At least 91 records · Page 5Linked to original sources

PubMed1987

Innervation of airway smooth muscle. Efferent mechanisms.

The classical view, with one excitatory (cholinergic) and one inhibitory (noradrenergic) component, of the innervation of airway smooth muscle is incomplete and at least two other, possibly peptidergic, types of innervation must be included when the innervation of airways is considered. A summary of these neuronal components is given in Fig. 1 and their possible origin is outlined. Besides the inhibitory noradrenergic innervation of the airways observed in some species, an inhibitory NANC (i-NANC) innervation has been demonstrated. The polypeptide, VIP, seems to be the most likely candidate for the neurotransmitter in the i-NANC innervation of the airways. The excitatory cholinergic innervation is present in the airways from the trachea down to the peripheral bronchi. In the guinea-pig bronchi an excitatory NANC (e-NANC) innervation has been demonstrated as well. The e-NANC nerves may correspond to chemosensitive primary afferent nerves with substance P or a related tachykinin as transmitter. When the innervation of airway smooth muscle of different mammalian species is compared it is evident that all nerve components except the cholinergic, show a considerable variability among species. The cholinergic innervation seems to be present in all mammalian species whereas the other components may be completely absent from some species. Distinct regional variations in the innervation of the airways may occur, which is exemplified by the distribution of the autonomic innervation in the guinea-pig tracheo-bronchial tree. Cholinergic neurotransmission in for example the guinea-pig and human airways can be modulated by NA via prejunctional inhibitory alpha 2-adrenoceptors. Furthermore, the e-NANC neurotransmission in the guinea-pig airways may be modulated by NA or by selective alpha 2-adrenoceptor agonists, acting via prejunctional inhibitory alpha 2-adrenoceptors. The clinical importance of the NANC innervation in relation to asthma is discussed. The i-NANC nerves may exert a modulating effect on bronchoconstriction, and a functional defect would presumably lead to an exaggerated response to constrictor stimuli. The e-NANC nerves in the airways may also be clinically relevant since the transmitter (tachykinins) from these nerves can produce bronchoconstriction and promote inflammation of the airway epithelium, either by direct mechanisms or indirectly by activation of mast cells, and thus contribute to the features of asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

Comparative studies on nerve- and noradrenaline-induced melanosome aggregation within different species of fish.

1. The aggregation of melanosomes within melanophores of the cuckoo wrasse (Labrus ossifagus; belonging to the family Labridae) has, on pharmacological grounds, been shown to be mediated by postsynaptic alpha 2-adrenoceptors which in turn act via an inhibitory control of adenylate cyclase. 2. In the present paper we have investigated some American species belonging to the Labridae, Haemulidae, Embiotocidae, Clinidae and Pleuronectidae. 3. In all instances, except in the case of sargo (Haemulidae), we could demonstrate that melanosome aggregation probably was mediated by postsynaptic alpha 2-adrenoceptors which mediate their effect by inhibiting the adenylate cyclase of the melanophores. 4. Although these receptors apparently, on pharmacological grounds, may be classified as alpha 2-adrenoceptors it was also concluded that there is a phylogenetic divergence among these receptors.

Adrenergic alpha-Antagonists↗

PubMed1987

Effects of some antihypertensive drugs on cutaneous blood flow and inflammatory skin responses following allergen challenge in guinea pigs.

The effects of the antihypertensive drugs clonidine, prazosin, and MK 422 (the active parent diacid of enalapril) were studied on the cutaneous blood flow and allergen evoked inflammatory skin reactions in ovalbumin sensitized guinea pigs. The hypotensive effect of the drugs did not significantly change the basal cutaneous blood flow at the time of allergen challenge. MK 422 (0.02 mg/kg) markedly enhanced the wheal and flare reaction following allergen challenge, whereas clonidine (0.005 and 0.05 mg/kg) inhibited the inflammatory response. Prazosin (0.03 mg/kg) did not significantly influence the wheal and flare reaction. Our results indicate that some antihypertensive drugs (clonidine) could be beneficial to antihypertensive patients with inflammatory diseases, while others (ACE-inhibitors) may enhance their inflammatory disorders.

Allergens↗

PubMed1987

Retention and subsequent liberation of glyceryl trinitrate in organ baths influences the relaxation of bovine mesenteric arteries contracted by various agents.

The present study compares the relaxant effect of glyceryl trinitrate (GTN) on isolated bovine mesenteric artery in commonly used organ baths made of glass and in disposable vials made of polyethylene, a material known to be inert to GTN. It is shown that the EC50-value for the GTN-induced relaxation is about 1000-fold lower when polyethylene vials are used. The study also shows that the reason for this is that the materials previously used in the experimental equipment retain and subsequently liberate GTN at re-use. In organ baths of glass with holders of acrylics, GTN concentrations of about 20 nM were found during equilibration, i.e. before start of the experiment. The vessel specimens become partly tolerant during equilibration in such organ baths and thus the vessels are less sensitive to GTN. The findings may explain the discrepancy between previous in vitro and in vivo studies. Low concentrations known to be effective in vivo have not been demonstrated to have a relaxant effect in earlier in vitro studies.

Animals↗

PubMed1987

Effects of clonidine on the dermal inflammatory cell response of experimental toxic and allergic contact reactions and intradermal hypersensitivity.

In previous studies, the alpha 2-adrenoceptor agonist clonidine has been shown to suppress the wheal and flare reaction in guinea pigs sensitized to ovalbumin. This phenomenon has been further studied with special reference to effects on the dermal inflammatory cell infiltrate and mast cells. Clonidine lessens the degranulation of mast cells seen in control untreated immediate hypersensitivity reactions. Less neutrophils and eosinophils arrive to the treated reactions. Basophils and mononuclear cells (chiefly lymphocytes) which characterize the late phase of the wheal and flare reaction were not influenced by clonidine. Clonidine had a possible minimal effect on allergic contact (delayed hypersensitivity) reactions. The toxic contact reaction to croton oil (nonspecific cutaneous inflammation) was not affected.

Animals↗

PubMed1987

Comparison of the effects of clonidine and guanfacine on the histamine liberation from human mast cells and basophils and on the human bronchial smooth muscle activity.

The inhibitory effects of clonidine and guanfacine on antigen-induced histamine release from human basophils and mast cells and on bronchial muscle tension were compared. Clonidine, but not guanfacine inhibited the antigen-induced histamine release from human basophils and mast cell preparations. This effect of clonidine was prevented by an H2-antagonist, cimetidine. Clonidine and guanfacine, like norepinephrine, inhibited the twitch contraction of electrically stimulated human segmental bronchi by stimulation of alpha 2-adrenoceptors. Clonidine and guanfacine had no effects on the basal bronchial muscle tone, but in very high concentrations they could reduce a carbacholine-induced bronchial tone. It is suggested that the inhibitory effects of clonidine on allergic reactions and on exicitatory nerve transmission in human airways may be useful in the treatment of asthmatic patients.

Adrenergic alpha-Agonists↗

PubMed1987

Development of tolerance towards glyceryl trinitrate in vitro. Low concentration induced tolerance and changes in cyclic guanosine-3',5'-monophosphate metabolism.

Bovine mesenteric arteries were exposed to glyceryl trinitrate (GTN) in vitro for 2 and 8 h in a low concentration (0.1 nmol/l), that equals the plasma concentrations reached by using GTN-discs in patients with angina pectoris. After reexposure to GTN a significantly reduced relaxant response was observed. In the concentration range 1 pmol/l to 10 nmol/l a 10-fold right shift of the concentration-effect curve was noted as compared to control vessels not previously exposed to GTN. The reduced relaxant response was accompanied by a significantly impaired ability to form cyclic guanosine-3',5'-monophosphate (cGMP). The results are interpreted as a development of tolerance towards GTN at the level of the vascular smooth muscle cell. A concentration of GTN (0.1 mmol/l) previously used to induce tolerance in vitro, produced a much more pronounced shift to the right of the concentration-response curve, especially in the concentration range 10 nmol/l to 0.1 mmol/l. This might indicate that tolerance to GTN can be induced by 2 different mechanisms, which in turn might be interpreted as the existence of 2 mechanisms of action by GTN in inducing vascular smooth muscle relaxation.

Animals↗

PubMed1987

Effects of different phosphodiesterase-inhibiting drugs on human pregnant myometrium: an in vitro study.

The phosphodiesterase (PDE)-inhibiting and smooth muscle relaxing effects of theophylline, enprofylline, papaverine and moxaverine have been studied in vitro on spontaneous contracting human, pregnant myometrium. All drugs showed a close correlation between the PDE-inhibiting and smooth muscle relaxing effect. The order of smooth muscle relaxing potency was papaverine greater than moxaverine greater than enprofylline greater than theophylline. The most potent PDE-inhibitors were moxaverine and papaverine with a 50% PDE-inhibiting concentration (IC50) of 3.3 and 3.8 microM as compared to the least potent PDE-inhibitor, theophylline, with an IC50 of 665 microM. It is concluded that PDE-inhibiting drugs show a close correlation between PDE-inhibiting and relaxing effect on spontaneously contracting pregnant myometrium and that the newly developed drug enprofylline might be of interest in the treatment of premature uterine contractions.

Female↗

PubMed1986

Inhibitory effects of clonidine on bronchospasm induced in guinea-pigs by vagal stimulation or antigen challenge.

The effects of clonidine on the bronchospastic responses induced by vagal stimulation or antigen challenge were studied in anaesthetized guinea-pigs. Electrical stimulation of the vagus nerves by 2-4 Hz induced a vigorous, mainly atropine-sensitive bronchoconstriction, which was strongly inhibited by clonidine (0.05 mg/kg i.v.). The inhibitory effect of clonidine was significantly reduced by the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg i.v.). Another series of experiments was done with ovalbumin-sensitized guinea-pigs. Respiratory anaphylaxis was induced by antigen inhalation resulting in an increase of pulmonary resistance from 100% (baseline) to about 190% in the control group. Animals pretreated with a clonidine aerosol (0.03%) showed a marked inhibition of the bronchospastic response. It is suggested that the inhibition of the bronchospastic responses induced by clonidine may be mediated by a stimulation of alpha 2-adrenoceptors, which exerts an inhibitory control of the excitatory vagal activity in the guinea-pig airways.

Anaphylaxis↗

PubMed1986

Effects of mepacrine and p-bromophenacyl bromide on anti-IgE and phospholipase A2-induced histamine release from human basophils.

Exposure of human basophils to purified phospholipase A2 caused a release of histamine, the process could be divided in one Ca2+-independent and one Ca2+-dependent stage. Low concentrations of mepacrine and p-bromophenacyl bromide (BPB) inhibited both phospholipase A2- and anti-IgE-induced histamine release. Mepacrine was more potent than BPB when the two-stage-method was used. The inhibition of mepacrine was most effective when the drug was added in the second Ca2+-dependent stage. The effect of mepacrine in the whole reaction of the anti-IgE-induced histamine release was biphasic and mepacrine was less effective than in the inhibition of the separated stages. The effect of BPB on the whole reaction was rather similar to mepacrine, although it was not biphasic. The results presented in this work confirm a previous hypothesis suggesting that activation of phospholipase A2 is an important step in the IgE-mediated histamine release process. The results also suggest that inhibition of histamine release due to inhibition of phospholipase A2 might be of therapeutical value as the system can be inhibited at very low drug concentrations.

Acetophenones↗

PubMed1986

Alpha-adrenergic receptors in human myometrium during pregnancy.

The distribution and mechanisms of alpha-adrenergic receptors have been studied in myometrial preparations from women delivered by cesarean section at term. With the use of the radioligand tritiated dihydroergocryptine, the number of alpha-adrenergic receptors was 210 fmol/mg of protein in the uterine fundus and 195 fmol/mg of protein in the lower uterine segment. Competition experiments showed that 60% of the alpha-adrenergic receptors had properties as alpha 1-adrenergic receptors and 40% as alpha 2-adrenergic receptors. In vitro tension studies verified the existence of physiologically active alpha 1- and alpha 2-adrenergic receptors in the myometrial preparations. alpha 2-Adrenergic receptor stimulation resulted in lowered levels of intracellular cyclic adenosine monophosphate. The intracellular cyclic adenosine monophosphate was further reduced by additional alpha 1-adrenergic receptor stimulation, probably secondary to an activation of calcium-calmodulin-dependent phosphodiesterase.

Adrenergic alpha-Antagonists↗

PubMed1986

The relaxant effect of glyceryltrinitrate on isolated human peripheral vein and its relation to cyclic GMP metabolism.

The relaxant effect of glyceryltrinitrate (GTN) on human vena saphena magna was studied in vitro. Vessels contracted by serotonin (0.25 microM) and phenylephrine (0.1 mM) were relaxed to the same extent (EC50 = 10 microM) by GTN, whereas in 100 mM K+-depolarized vessels the relaxation was significantly lower. The relaxant effect produced by GTN was preceded by an elevation of cyclic guanosine-3',5'-monophosphate (cGMP). For 0.1 mM GTN there was a 3-fold increase in cGMP after 3 min. A correlation between relaxation and increase in cGMP was established. When GTN was combined with dipyridamole (5 microM) the relaxant effect of GTN was significantly greater (EC50 = 0.1 microM). Phosphodiesterase inhibition, as a possible mechanism behind the observed better relaxation for the combination (GTN+dipyridamole), is briefly discussed. In conclusion, the relaxant effect of GTN on isolated human vena saphena magna seems to be dependent on the contractile stimuli used, increased by the addition of DIP and to be mediated via cGMP.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1986

Development of tolerance to glyceryl trinitrate in an isolated human peripheral vein and its relation to cyclic GMP metabolism.

Human peripheral vein (v. saphena magna) was exposed in vitro to glyceryl trinitrate (GTN) 0.1 mM for 1 h. The subsequent relaxant effect of GTN (10nM-0.1 mM) on vessels contracted by serotonin (0.25 microM) was significantly reduced on vessels preexposed to GTN as compared to control vessels, indicating a development of partial tolerance as far as the vascular smooth muscle relaxant effect is concerned. The impaired relaxant effect was paralleled by a reduced increment of intracellular cyclic GMP. This is, in turn, probably a consequence of both a diminished guanylate cyclase activity and an elevated phosphodiesterase activity in the GTN-tolerant vessels. The relaxant activity as well as the level of intracellular cyclic GMP were restored in GTN-tolerant vessels by dipyridamole (5 microM), an agent with phosphodiesterase inhibiting properties.

Cyclic GMP↗

PubMed1986

The effect of inhaled clonidine in patients with asthma.

To study the effect of inhaled clonidine on broncho-obstruction in asthmatics, 10 patients with extrinsic asthma were broncho-provoked twice with an allergen that had been shown to give positive skin prick test results. Before the provocations, saline or clonidine (75 micrograms) was inhaled via a DeVilbiss no. 40 nebulizer. Clonidine slightly improved the basal respiratory function without significantly influencing the blood pressure. There was a reduction in the allergen-evoked broncho-obstruction by 42 to 65% after pretreatment with clonidine. The eosinophilic leukocytes in peripheral blood had a slight tendency to leave the circulatory system during the provocation preceded by the clonidine treatment. These data add further evidence to the finding that clonidine may be of interest in the treatment of broncho-obstructive diseases.

Administration, Intranasal↗

PubMed1986

Action spectra of photoactivated cyclic GMP metabolism and relaxation in bovine mesenteric artery.

Strips of bovine mesenteric arteries, brought to sustained contraction by addition of 3.0 microM phenylephrine, relaxed during exposure to shortwave light. The action spectrum of the photorelaxation was characterized by most effectiveness of relaxation in the range of 360 to 400 nm; on the contrary, shortwave light of 280 to 300 nm increased the tension. The photo-induced relaxation was accompanied by an increase in the cGMP level, measured 30 sec after the onset of radiation, and the action spectrum of the increase in cGMP seemed to coincide fairly well with the action spectrum of relaxation. Both the increase in cGMP and relaxation in response to increasing light intensity at 400 nm fitted the rectangular hyperbolic equation. The K values (the intensity which gave half maximal response) for cGMP increase and relaxation, respectively, obtained by non-linear least square regression analysis, were found to assume very close values (1.3 mW/cm2 for cGMP increase and 1.5 mW/cm2 for relaxation). The action spectrum of the crude soluble guanylate cyclase (GC) activity displayed a peak around 400 nm. Our results suggest that there is a close association between photo-induced increase in cGMP and relaxation, probably as a result of interaction between shortwave light and the heme moiety of GC.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1986

Experimental studies on the mechanism of glyceryl trinitrate-tolerance and dependence.

Tolerance to glyceryl-trinitrate (GTN) in arteries and veins was studied in different in vitro and in vivo models. The development of GTN tolerance was associated with a down-regulation of the cGMP system, i.e. an impairment of the nitrocompound-dependent activation of guanylate cyclase and an increase of the cGMP-phosphodiesterase activity. We suggest that a decreased function of the cGMP system might cause an impairment of the negative feedback loop involving cGMP in blood vessels, and a concomitant supersensitivity to contractile stimuli.

Animals↗

PubMed1985

The effect of pertussis toxin on alpha-2-adrenoceptor-mediated pigment migration in fish melanophores.

The aggregation of melanin-granules within fish pigment cells (melanophores) can be elicited either by electrical stimulation of intrinsic nerves or by the addition of adrenergic agonists. The pigment aggregation seems to be mediated by alpha-2-adrenoceptors. In this investigation we have used various agonists and antagonists (noradrenaline, (+)- and (-)-adrenaline, isoprenaline, yohimbine and prazosin) to further characterize the pigment-aggregating receptor of Labrus ossifagus. All the results obtained support the notion of alpha-2-adrenoceptor-mediated pigment aggregation. The pertussis toxin, islet-activating protein (IAP), is known to inhibit the alpha-2-adrenoceptor-mediated signal transduction in mammals. We have used IAP to investigated whether fish melanophore alpha-2-adrenoceptors are also inhibited by this toxin. We found that IAP inactivated the alpha-2-adrenoceptor-mediated pigment aggregation in a dose-dependent manner. The inhibitory IAP-effect had a remarkably short onset-time in the melanophores (maximal effect was obtained within 10 min of incubation). Interestingly, binding of an agonist (noradrenaline) to the receptors prevented IAP from exerting its inhibitory action, whereas binding of an antagonist (yohimbine) gave no protection against the IAP-inactivation. In conclusion, the pigment-aggregating receptors of melanophores of L. ossifagus are very similar to the mammalian alpha-2-adrenoceptors. It is possible to inactivate the melanophore receptor system with IAP and this inactivation has a remarkably short onset-time. Stimulation of the alpha-2-adrenoceptors prevents IAP from inactivating the receptor system.

Adrenergic alpha-Agonists↗

PubMed1985

Beta-adrenergic receptors in human myometrium during pregnancy: changes in the number of receptors after beta-mimetic treatment.

The concentration of available beta-adrenoceptors has been studied in the myometrium of women treated with terbutaline for premature uterine contractions and in an untreated control group. Myometrial strips were taken at cesarean section from the lower uterine segment and the uterine fundus. The concentration of beta-adrenoceptors was determined with a radioligand binding assay. In untreated women we found no difference in the concentration of beta-adrenoceptors in the uterine fundus compared to that in the lower uterine segment. The cyclic adenosine monophosphate production after beta-adrenoceptor agonist stimulation in vitro was equal in both locations. In the terbutaline-treated women, the binding site concentrations in both the fundus and lower uterine segment were lower compared to those in the control group. The decrease was most pronounced in the fundus where receptor concentration was only half that found in the control group. The results suggest that treatment with beta-mimetics causes a desensitization in the beta-adrenoceptor system of human myometrium during pregnancy. This desensitization may partly explain the limited duration of the relaxant effect of beta-mimetics often seen in the treatment of preterm labor.

Cyclic AMP↗