bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four motor effects of capsaicin on guinea‐pig distal colon
Authors: Maggi Carlo Alberto , Meli Alberto , Santicioli Paolo 
Published: July 2012

The motor effects of capsaicin on the guinea‐pig distal colon have been investigated in vivo and in vitro.
Capsaicin (0.1–10 μg kg−1 i.v.) produced a transient relaxation which was reduced by pretreatment with capsaicin itself, atropine, hexamethonium, phentolamine or guanethidine and almost abolished by tetrodotoxin (TTX). Topically applied capsaicin produced a transient inhibition of tone and spontaneous activity prevented by topically applied TTX.
In isolated preparations of distal colon, capsaicin produced a transient, TTX‐ and atropine‐sensitive contraction which was followed by a depression of the contractile activity. The depressant effect was unaffected by atropine plus guanethidine but was greatly reduced by TTX, indicating activation of intramural non‐adrenergic, non‐cholinergic (NANC) mechanisms. The depressant effect on the first exposure to capsaicin (1 μm) was greater than that produced by a second, third or fourth exposure.
In preparations excised from capsaicin‐pretreated animals, capsaicin (1 μm) only produced an inhibitory effect on spontaneous contractions. Desensitization did not occur to this inhibitory effect.
In preparations pre‐exposed to capsaicin (1 μm, 1 h before), capsaicin (1–30 μm) produced a concentration‐related inhibition of spontaneous contractions (IC50 = 19 μm) and of the high K+ ‐ induced tonic contraction (IC50 = 23 μm). A similar effect on spontaneous motility was produced by capsaicin in colonic segments excised from capsaicin‐pretreated guinea‐pigs (IC50 = 16 μm) or guinea‐pigs treated with TTX (IC50 = 20 μm).
It is concluded that, in vivo, capsaicin activates inhibitory reflexes, presumably due to stimulation of primary afferent fibres. This effect involves, at least in part, activation of sympathetic nerves to this organ. The contractile effect of capsaicin on the isolated colon involves activation of intramural cholinergic neurones, whereas the TTX‐sensitive component of the inhibitory effect involves either release of an inhibitory transmitter through an axon reflex arrangement or activation of NANC neurones. In addition, at high concentrations capsaicin produces a direct depression of smooth muscle contraction.
Evidence that locus coeruleus is the site where clonidine and drugs acting at α1‐ and α2‐adrenoceptors affect sleep and arousal mechanisms
Authors: De Sarro G.B. , Ascioti C. , Froio F. , Libri V. , Nisticò G. 
Published: July 2012

The behavioural and electrocortical (ECoG) effects of clonidine were studied after microinjection into the third cerebral ventricle, or microinfusion into some specific areas of the rat brain rich in noradrenaline‐containing cell bodies (locus coeruleus) or into areas receiving noradrenergic terminals (dorsal hippocampus, amygdaloid complex, thalamus, frontal and sensimotor cortex).
The ECoG effects were continuously analysed and quantified by means of a Berg‐Fourier analyser as total power and as power in preselected bands of frequency.
Clonidine (9.4 to 75 nmol) given into the third cerebral ventricle produced behavioural sedation and sleep and a dose‐dependent increase in ECoG total voltage power as well as in the lower frequency bands. Much lower doses were required to produce similar behavioural and ECoG spectrum power effects after either unilateral or bilateral microinfusion of clonidine into the locus coeruleus.
Doses of clonidine equimolar to those given into the third cerebral ventricle, were almost ineffective in inducing behavioural and ECoG sleep after their microinfusion into the dorsal hippocampus. In addition, a dose (0.56 nmol) of clonidine which, given into the locus coeruleus, produced marked behavioural sleep and ECoG synchronization, lacked effects when given into the ventral or anterior thalamus, into the amygdaloid complex or onto the frontal and sensimotor cortex.
The behavioural and ECoG spectrum power effects of clonidine given into the third cerebral ventricle or into the locus coeruleus were prevented by antagonists of α2‐adrenoceptors but not by α1‐adrenoceptor antagonists.
Intraventricular microinjection, or microinfusion into the locus coeruleus, of yohimbine, a selective α2‐adrenoceptor antagonist, produced behavioural arousal, increase in locomotor and exploratory activity, tachypnoea and ECoG desynchronization with a significant reduction in total voltage power. Similar stimulatory effects were also observed after microinjection of phentolamine into the same sites.
No significant effects on behaviour and ECoG activity were evoked after intraventricular injection or microinfusion into the locus coeruleus of prazosin or methoxamine.
Stress induced ACTH release in capsaicin treated rats
Authors: Amann Rainer , Lembeck Fred 
Published: July 2012

The plasma concentrations of adrenocorticotropic hormone (ACTH) in rats pretreated with capsaicin as neonates were compared with those of control rats pretreated with the capsaicin vehicle. Capsaicin pretreatment has been shown earlier to abolish the increase in plasma ACTH concentration induced by cold stress while not affecting that induced by restraint stress.
In the present experiments rats pretreated with capsaicin showed the same increase in plasma ACTH concentration in response to an i.v. infusion of ovine‐corticotropin releasing factor as control rats pretreated with the capsaicin vehicle.
Intraperitoneal injection of formalin, surgical stress and intravenous infusion of (–)‐isoprenaline increased plasma ACTH concentrations in control rats. In capsaicin pretreated rats the increase in plasma ACTH was significantly attenuated.
It is concluded that capsaicin‐sensitive sensory neurones mediate the activation of pituitary ACTH secretion in response to somatosensory stimuli. The function of the corticotroph cells of the anterior pituitary is not impaired by capsaicin treatment.
The protective effects of sulphasalazine against ethanol‐induced gastric damage in rats
Authors: Cho C.H. , Ogle C.W. , Sevilla E.L. 
Published: July 2012

The inhibitory action of sulphasalazine on ethanol‐induced gastric damage was studied in rats.
Sulphasalazine (62.5 or 125 mg kg−1, s.c.) did not affect basal gastric acid secretion but increased pepsin output.
Ethanol (40% v/v, 10 ml kg−1, p.o.) produced severe gastric glandular mucosal damage and lessened the stomach emptying rate of resin pellets, but it increased the levels of prostaglandin E2 (PGE2)‐like activity in the glandular mucosa.
Sulphasalazine markedly prevented ethanol‐induced damage and significantly elevated gastric wall mucus levels both in basal conditions and in the presence of ethanol.
Sulphasalazine caused a small insignificant increase in mucosal PGE2 levels in both control and ethanol‐treated rats. The drug significantly increased mucosal PGE2 levels in indomethacin‐treated animals, but did not prevent indomethacin‐induced mucosal damage.
Sulphapyridine but not 5‐aminosalicylic acid, constituents of sulphasalazine, showed a similar antilesion action to the parent drug, and prevented gastric wall mucus depletion in ethanol‐treated animals.
This study elucidates the protective effects of sulphasalazine against ethanol‐induced gastric lesions. The antagonistic action appears to be mediated, at least partly, through the preservation of gastric wall mucus by sulphapyridine.
Positive inotropic and chronotropic effects of trypsin and some other proteolytic enzymes in the guinea‐pig heart
Authors: Imai Shoichi , Kawada Tomie , Kimura Takahito , Ohta Hideo , Nakazawa Mikio , Yoshida Yutaka 
Published: July 2012

In atrial preparations of the young guinea‐pig (body weight 150–250 g), five proteolytic enzymes (trypsin, chymotrypsin, bacterial‐Al‐proteinase (nagarse), bromelain and kallikrein) produced concentration‐dependent positive inotropic and chronotropic effects, while they exerted only minimal effects on the papillary muscle preparations.
To characterize the effects, further experiments were conducted in atrial preparations using trypsin. There was a strong tendency for tachyphylaxis: a second exposure to the same concentration of trypsin resulted in considerably smaller positive inotropic and chronotropic effects. The positive inotropic and chronotropic effects of this substance were not affected by propranolol (5 × 10−7 m). However, an accumulation of cyclic AMP was observed and the positive inotropic and chronotropic effects were potentiated by aminophylline (10−4 m) in association with an augmentation of the accumulation of cyclic AMP. In preparations partially depolarized with high K+ (22 mm) medium (contractions ceased under this condition) trypsin 100 μg ml−1 reinstated the contraction. Treatment of the preparation with aprotinin (200 u ml−1) resulted in a strong inhibition of the positive inotropic and chronotropic effects.
Islet activating protein (IAP), a specific inhibitor of the ‘inhibition specific’ guanine nucleotide binding regulatory protein of the adenylate cyclase system, did not produce significant inhibition of the positive inotropic and chronotropic effects of trypsin, whereas it produced a complete inhibition of the negative inotropic and chronotropic effects of carbachol.
These results suggest that the positive inotropic and chronotropic effects of proteolytic enzymes are intimately connected with the proteolytic activities through which adenylate cyclase is activated to produce an accumulation of cyclic AMP within the myocardium. The destruction of the inhibition specific' guanine nucleotide regulatory protein of the adenylate cyclase was not substantiated as a mechanism of activation of the adenylate cyclase.
Apparent affinity of some 8‐phenyl‐substituted xanthines at adenosine receptors in guinea‐pig aorta and atria
Authors: Collis M.G. , Jacobson K.A. , Tomkins D.M. 
Published: July 2012

Some 8‐phenyl‐substituted, 1,3 dipropyl xanthines have previously been demonstrated to have a 20–400 fold greater affinity for A1 binding sites in rat CNS membranes than for A2 adenosine receptors in intact CNS cells from guinea‐pigs. In the present study these compounds (1,3, dipropyl‐8‐phenylxanthine: DPPX; 1,3 dipropyl‐8‐(2 amino‐4‐chlorophenyl) xanthine: PACPX; 8‐(4‐(2‐aminoethyl)amino) carbonyl methyl oxyphenyl)‐1,3‐dipropylxanthine: XAC; and d‐Lys‐XAC) together with two that have not been reported to exhibit A1‐receptor selectivity (8‐(p‐sulphophenyl)theophylline: 8‐PST; 8‐(4‐carboxy methyl oxyphenyl)‐1,3‐dipropylxanthine: XCC) have been evaluated as antagonists of the effects of 2‐chloroadenosine in two isolated cardiovascular tissues.
The isolated tissues used were guinea‐pig atria (bradycardic response) and aorta (relaxation), which are thought to possess A1 and A2 adenosine receptors, respectively.
All the xanthines antagonized responses evoked by 2‐chloroadenosine in both tissues but did not affect responses evoked by acetylcholine (atria) or sodium nitrite (aorta).
The xanthines, 8‐PST, XAC, d‐Lys XAC, XCC and DPPX appeared to be competitive antagonists of the effects of 2‐chloroadenosine, as Schild plot slopes did not differ significantly from unity. The 1,3‐dipropyl substituted compounds had pA2 values from 6.5 to 7.4 and were more potent than the 1,3 dimethyl substituted 8‐PST (pA2 4.9 to 5).
For individual xanthines, there was no difference between pA2 values obtained in the atria and in the aorta.
Responses evoked by 2‐chloroadenosine in atria and aorta were antagonized to a similar degree by PACPX (1 μm). The agonist dose‐ratio evoked by 10 μm PACPX was no greater than that evoked by 1 μm of the xanthine in both tissues. This was probably a consequence of the limited aqueous solubility of PACPX.
These results fail to demonstrate A1 receptor selectivity for DPPX, XAC, d‐Lys XAC or PACPX in tissues from the guinea‐pig. The A1 selectivity previously found for these compounds may therefore be due to their high affinity for binding sites in rat CNS cell membranes.
The effects of nitroglycerin on exercise‐induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine
Authors: Schneider W. , Krumpl G. , Mayer N. , Raberger G. 
Published: July 2012

Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise‐induced regional myocardial dysfunction in conscious dogs.
We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy.
Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end‐diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area.
DHE (5 μg kg−1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function.
After pretreatment with DHE, infusion of nitroglycerin (15 μg kg−1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end‐diastolic pressure and an increase in left ventricular dp/dtmax.
These results suggest that DHE will not worsen exercise‐induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE.
Effect of platelet agonists on airway reactivity and intrathoracic platelet accumulation
Authors: Robertson D.N. , Page C.P. 
Published: July 2012

Intravenous infusion of platelet activating factor (Paf), adenosine diphosphate (ADP), collagen and the thromboxane‐mimetic U46619 induced a dose‐related accumulation of 111indium‐labelled platelets into the thoracic region of anaesthetized guinea‐pigs.
Intravenous infusion of Paf increased the reactivity of the airways to the spasmogen histamine. Such changes were not observed following treatment with ADP, collagen or U46619.
Paf‐induced bronchial hyperreactivity is not secondary to pulmonary platelet recruitment, changes in basal lung function or cardiovascular changes.
Paf‐induced bronchial hyperreactivity is not dependent upon the endogenous generation of ADP or thromboxane.
The influence of atherosclerosis on the mechanical responses of human isolated coronary arteries to substance P, isoprenaline and noradrenaline
Authors: Berkenboom Guy , Depierreux Michel , Fontaine Jeanine 
Published: July 2012

The responses to substance P, isoprenaline and noradrenaline were observed on human isolated coronary arteries removed from 30 human hearts, and were classified according to the age of the hearts, the presence or absence of cardiac failure and the degree of atherosclerosis.
The endothelium‐dependent vasodilator, substance P (0.1 μm), relaxed rings precontracted with prostaglandin F2α, (PGF2α, 1 μm) when they were devoid of atherosclerosis. The presence of moderate or severe lesions of atherosclerosis abolished this response. There was no difference in the response, related to either the age of the hearts or to the presence or absence of cardiac failure.
The dose‐response curves to isoprenaline (an endothelium‐independent vasodilator) were also markedly altered by the presence of atherosclerotic lesions, while aging and the presence of cardiac failure did not alter the maximal relaxation. These last 2 factors induced only a rightward shift of the dose‐response curves.
On severely atherosclerotic rings, β‐adrenoceptor‐mediated responses were so altered that the effect of noradrenaline was wholly vasoconstrictor (via α‐adrenoceptors). This response was not modified after pretreatment with atenolol (10 μm).
It is concluded that atherosclerosis in human coronary arteries, induces alterations in the responses to substance P and to β‐adrenoceptor agonists. The β‐adrenoceptor‐mediated relaxations seem more influenced by the presence of atherosclerosis than they are by aging or by the down‐regulation induced by cardiac failure. Conversely, the α‐adrenoceptor responses appear to be well preserved.
Procoagulant activity of platelet arachidonic acid metabolites
Authors: Barrowcliffe T.W. , Edwards S.J. , Gray Elaine , Kerry P.J. 
Published: July 2012

Arachidonate metabolites have been extracted from indomethacin‐treated human platelets after incubation with arachidonic acid.
After separation from platelet phospholipids, the extracts promoted the generation of large amounts of thrombin in normal plasma, but not in plasma devoid of lipoproteins.
The procoagulant activity was associated with a minor component of the mixture, which was active at concentrations below 10 μg ml−1.
The activity was similar to that of autoxidised arachidonic acid previously described.
Platelet arachidonic acid metabolites could play a role in the coagulation system.
Antisecretory and antiulcer effect of the H2‐receptor antagonist famotidine in the rat: comparison with ranitidine
Authors: Scarpignato Carmelo , Tramacere Roberto , Zappia Luciana 
Published: July 2012

The effects of the new H2‐receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally‐induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound.
Both compounds inhibited acid secretion in a dose‐dependent manner. Calculated ED50 values were 0.80 and 6.84 mg kg−1 for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs.
The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect.
Famotidine reduced, in a dose‐dependent manner, ulcer incidence in stomachs of dimaprit‐treated rats and in duodena of cysteamine‐treated animals with a potency respectively 2 and 7 times higher than that of ranitidine.
Famotidine is therefore an effective antisecretory and untiulcer compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs.
Protein kinase C activation and α2‐autoreceptor‐modulated release of noradrenaline
Authors: Allgaier Clemens , Hertting Georg , Huang Hua Yu , Jackisch Rolf 
Published: July 2012

Effects of phorbol esters on the evoked noradrenaline release were studied in slices of the rabbit hippocampus, labelled with [3H]‐noradrenaline, superfused continuously with a medium containing the reuptake inhibitor cocaine and stimulated electrically for 2 min (stimulation parameters: 2 ms, 24 mA, 5 V cm−1, 3 or 0.3 Hz).
The electrically‐evoked overflow of [3H]‐noradrenaline in the slices was increased in a concentration‐dependent manner by the protein kinase C (PKC) activators 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) and 4β‐phorbol 12,13‐dibutyrate (4β‐PDB). Phorbol esters, which do not activate PKC, 4‐O‐methyl‐TPA and 4α‐PDB, showed no effect on neurotransmitter release. The effect of 4β‐PDB was abolished in the presence of tetrodotoxin and in the absence of calcium. The PKC inhibitor polymyxin B inhibited the evoked noradrenaline release.
In the presence of 4β‐PDB the inhibitory effects of the α2‐adrenoceptor agonist clonidine or the facilitatory effects of the α2‐adrenoceptor antagonist yohimbine seemed to be modified only by changes in the concentration of noradrenaline in the synaptic region. At a stimulation frequency of 3 Hz the inhibitory action of clonidine was reduced whereas the facilitatory effect of the yohimbine was even slightly enhanced by the phorbol ester. At 0.3 Hz and in the presence of 4β‐PDB the effect of clonidine remained and that of yohimbine was strongly enhanced.
Pretreatment of the slices with islet‐activating protein or N‐ethylmaleimide significantly reduced the enhancement of noradrenaline release caused by 4β‐PDB. It is possible that a regulatory N‐protein is involved in steps following PKC activation.
These results suggest that PKC participates in the mechanism of action‐potential‐induced noradrenaline release from noradrenergic nerve terminals of the rabbit hippocampus and that effects on the autoinhibitory feedback system were not responsible for the 4β‐PDB‐induced increase of neurotransmitter release.
Airways hyperreactivity and bronchoconstriction induced by vanadate in the guinea‐pig
Authors: Nayler Ross A. , Mitchell Howard W. 
Published: July 2012

The characteristics of vanadate‐induced bronchoconstriction and airways hyperreactivity were observed in spontaneously breathing anaesthetized guinea‐pigs by measurement of airways resistance (Raw) and dynamic lung compliance (Cdyn). Vanadate (0.3–3 mg kg−1 i. v. over 25 min) increased Raw and decreased Cdyn in a reversible, dose‐related manner. This action (1 mg kg−1 vanadate) was not inhibited by atropine (1 mg kg−1 i.v.), propranolol (1 mg kg−1 i.v.) or bilateral vagotomy, suggesting a direct effect on the airways smooth muscle.
An aerosol of vanadate (10% w/v in H2O) for 3 min decreased Cdyn by 19.5% (P < 0.05, n = 6) but caused no change in Raw.
Histamine (3 μg kg−1 i.v.) caused a bronchoconstriction which was enhanced by vanadate in a dose‐related manner. This hyperreactivity (after 1 mg kg−1 i.v. vanadate) was unchanged after propranolol or bilateral vagotomy, but was partly blocked by atropine (enhancement by vanadate of the Cdyn change to histamine was diminished, P < 0.02, n = 3).
Bronchoconstrictor responses to acetylcholine (6 μg kg−1 i.v.) and 5‐hydroxytryptamine (6 μg kg−1 i.v.) were also enhanced by vanadate (1 mg kg−1 i.v.). Hyperreactivity after vanadate to the three bronchoconstrictors tested continued during vanadate infusion and was reversed 45 min after cessation of infusion.
Histamine (3 μg kg−1 i.v.) caused a transient tachypnoea which was also enhanced by vanadate (0.3–3 mg kg−1 i.v.), in a dose‐related manner, in association with the increased reactivity of the airways (r = 0.66, n = 11).
It is concluded that vanadate‐induced airways hyperreactivity is non‐vagal (efferent) and largely non‐cholinergic in origin and appears to involve an action of vanadate within the lung itself.
The effect of enkephalins and of β‐endorphin on the hypertensive response to physostigmine in the rat
Authors: Varagić V.M. , Stojanović Vedrana 
Published: July 2012

Intracarotid injection of [Leu]enkephalin and [Met]enkephalin produced a dose‐dependent biphasic change in blood pressure of the rat consisting of an initial shortlasting fall followed by a longlasting increase of blood pressure. Naloxone consistently depressed or abolished the effects of enkephalins on blood pressure.
Intracarotid injection of β‐endorphin only occasionally produced a hypotension, or did not produce any change in the blood pressure of the rat.
All three opioids ([Leu]enkephalin, [Met]enkephalin and β‐endorphin) significantly depressed or abolished the hypertensive response to intravenous injection of physostigmine. This depressive action of opioids was easily reversed by naloxone.
It is concluded that opioids depress the central cholinergic link implicated in the hypertensive response to physostigmine most probably by inhibiting acetylcholine and/or noradrenaline release in the structures relevant for the action of physostigmine on blood pressure of the rat. This interaction is realized through the activation of opioid receptor(s).