Search PubMed⌕ Search

Biomedical subjects

C A Maggi

Publications and source records attributed to C A Maggi.

At least 595 records · Page 33Linked to original sources
PubMed1982

Age-related protective role of parasympathetic nervous system against hypercalcaemia-induced ventricular arrhythmias in the rat.

Time of appearance of extrasystoles, ventricular fibrillation, and cardiac arrest were monitored in urethane-anaesthetized rats of different ages following CaCl2 infusion. Ca++ required to produce ventricular arrhythmias was significantly higher in younger than in older animals. Bilateral vagotomy or atropine treatment significantly reduced Ca++ requirements for production of arrhythmias in younger but not in older animals. These findings support the hypothesis of vagally mediated age-related antagonism toward Ca++-induced ventricular arrhythmias. This suggests that young subjects are less prone to develop ventricular rhythm disturbances as a result of hypercalcaemic states.

Age Factors↗
PubMed1982

The effects of nifedipine and verapamil on spontaneous and carbachol-stimulated contractions of rat urinary bladder "in vivo".

The effects of nifedipine and verapamil on spontaneous and carbachol-induced contractions of rat urinary bladder have been studied after intravenous administration. Both nifedipine and verapamil delayed the onset of spontaneous contractions in a dose-dependent manner, but nifedipine on the contrary of verapamil only slightly antagonized the intensity of spontaneous contractions and of carbachol contracture. These results suggest that the effects of verapamil on rat urinary bladder "in vivo" are different from those of nifedipine.

Animals↗
PubMed1981

The anesthetized guinea pig as a versatile pharmacological test object.

An anesthetized animal preparation suitable for testing the pharmacological properties of a variety of potentially effective new compounds is described. The advantage of such a procedure as an useful tool to determine the pharmacodynamic profile of the new agents is described in detail.

Adrenergic beta-Antagonists↗
PubMed1981

The role of the local anaesthetic properties of beta-adrenoceptor blocking agents in antagonizing CaCl2-induced arrhythmias in the rat.

1 Eight beta-adrenoceptor blocking agents were compared for their ability to antagonize arrhythmias induced by bolus injections of CaCl2 in rats. 2 Only those beta-blockers possessing local anaesthetic properties were effective in antagonizing this type of arrhythmia and there was a highly significant correlation between antiarrhythmic and local anaesthetic properties. 3 Effects on adrenoceptors seem to play only a minor role in the genesis of this type of arrhythmia.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Conformational rigidity versus flexibility in a novel peptidic neurokinin A receptor antagonist.

Neurokinin A receptor antagonists have been proposed as a new class of drugs for several applications in humans (asthma, intestinal motility, etc.). The rational design, synthesis, structural characterization and biological activity evaluation of a new potent, highly selective, long-lasting, peptide-based receptor antagonist are reported. The structure-activity relationship indicates that the conformational rigidity determines potency, specificity and especially the long life of the molecule in the living body. MEN10627 is the prototype of a new class of cyclic, peptide-based, neurokinin A receptor antagonists and it is a suitable candidate for clinical testing in humans.

Amino Acid Sequence↗
PubMedDate not supplied

Vesico-inhibitory responses and capsaicin-sensitive afferents in rats.

(1) The effect of perineal pinching and distension of a balloon inserted into the colon on motility of the urinary bladder has been investigated in adult urethane-anesthetized rats pretreated with capsaicin (50 mg/kg s.c.) or its vehicle 4 days before the experiments. (2) At bladder volumes which were sufficient to elicit reflex micturition, perineal pinching or colonic distension transiently inhibited the ongoing bladder voiding contraction. The somato-vesical inhibitory response was markedly reduced or even abolished by division of pudendal nerves. Neither the somato-vesical nor the colovesical inhibitory response were modified by desensitization with systemically administered capsaicin. (3) Intraurethral administration of capsaicin produced a transient inhibition of the reflexly-activated bladder contractions. A second administration of the drug was less effective, indicating desensitization. Intravenously administered capsaicin had a similar inhibitory effect on bladder motility. (4) The vesico-inhibitory response produced by intraurethral administration of capsaicin was not affected by phentolamine, propranolol, guanethidine, picrotoxin or naloxone, while it was greatly reduced or even abolished by bilateral section of the pudendal nerves. (5) These findings provide evidence that capsaicin-sensitive chemoreceptors in the rat urethra are involved in generating a vesico-inhibitory response via pudendal nerves. On the other hand, no evidence was found for the participation of capsaicin-sensitive nerves in the generation of the somato- or colo-vesical inhibitory response.

Animals↗
PubMedDate not supplied

Tachykinin receptors mediate atropine-resistant rat duodenal reflex contractions in vivo.

The study aimed to establish the possible role of tachykinins as mediators of atropine-resistant reflex contractions evoked by balloon distension in the proximal duodenum of urethane-anesthetized, guanethidine (34 mumol/kg s.c.)-pretreated rats. Distension of the balloon with a small amount (0.2-0.3 ml) of saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in amplitude) which were promptly suppressed by either atropine (3 mumol/kg i.v.) or hexamethonium (28 mumol/kg i.v.). Despite the continuous i.v. infusion of atropine (2 mumol/h), low-amplitude rhythmic phasic contractions recovered, which were promptly suppressed by hexamethonium, to indicate the involvement of an atropine-resistant excitatory reflex. The amplitude of these atropine-resistant contractions was increased to about 4-5 mmHg by further distension of the balloon (0.4-0.6 ml) : under these conditions, the atropine-resistant contractions undergo a progressive fading. The fading was prevented by i.v. administration of the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME, 55 mumol/h), to provide a suitable baseline (amplitude of contractions was 7-8 mmHg) for studying the effect of tachykinin receptor antagonists. I.v. administration of the selective tachykinin NK2 receptor antagonists, MEN 10,627 (10-100 nmol/kg) and SR 48968 (100-300 nmol/kg) or of the selective NK1 antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal contractions induced by acetylcholine (5.5 mumol/kg i.v.), produced a prompt and long lasting suppression of the atropine-resistant reflex duodenal contractions produced by balloon distension in urethane-anesthetized rats, whilst SR-48965 (300 nmol/kg), the enantiomer of SR-48968 devoid, of NK2 receptor blocking activity, was without effect. I.v. administration of the selective NK1 receptor agonists [Sar9] substance P sulfone and septide or of the NK2 receptor selective agonist, [beta Ala8] neurokinin A(4-10) produced dose-dependent contractions of the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal contractions produced by [Sar9] substance P sulfone and septide without affecting those produced by [beta Ala8] neurokinin A(4-10). On the other hand, MEN 10,627 (30-100 nmol/kg i.v.) and SR 48968 (100-300 nmol/kg i.v.) but not SR 48965 (300 nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced by both the selective NK2 and NK1 receptor agonists. We conclude that endogenous tachykinins are involved in mediating atropine-resistant reflex contractions evoked by distension of the rat duodenum in vivo: both NK1 and NK2 receptors are activated by endogenous ligands to produce NANC contractions of rat duodenum in vivo. However, the contractile response to i.v. administered NK1 receptor agonists, [Sar9] substance P sulfone and septide, may involve the release of mediators producing smooth muscle contraction via NK2 receptors.

Analysis of Variance↗
PubMedDate not supplied

The effect of thiorphan and epithelium removal on contractions and tachykinin release produced by activation of capsaicin-sensitive afferents in the guinea-pig isolated bronchus.

(1) We have studied the effect of epithelium removal (rubbing) and the endopeptidase 24.11 inhibitor, thiorphan, on the contractile response of the guinea-pig isolated bronchi (atropine and indomethacin in the bath) produced by electrical field stimulation, capsaicin or exogenously administered tachykinins (substance P and neurokinin A). (2) The response to field stimulation, thought to involve release of endogenous tachykinins, was potentiated by thiorphan in both epithelium-free and intact bronchi. However, at low frequencies (1-5 Hz), the effect of thiorphan was more evident in intact preparations. (3) The response to capsaicin was enhanced by both epithelium removal and thiorphan administration. (4) The response to exogenous substance P or neurokinin A was potentiated by thiorphan both in epithelium-free and intact bronchi. (5) Capsaicin (1 microM) evoked a consistent release of substance P-like immunoreactivity (determined by radioimmunoassay) and tachykinin-like immunoreactivity (determined by a novel immunoenzyme assay), which was enhanced by thiorphan in both epithelium-free and intact bronchi. (6) These findings suggest that a thiorphan-sensitive mechanism, presumably 'enkephalinase' (endopeptidase 24.11), plays a major role in inactivating endogenous tachykinins released from sensory nerves and that this enzymatic activity is still present after removal of the bronchial epithelium.

Animals↗
PubMedDate not supplied

Tachykinins protect against ethanol-induced gastric lesions in rats.

Subcutaneous pretreatment of rats with neurokinin (NK) A or the fragment NKA(4-10) reduced the degree of gastric lesions induced by oral administration of 96% ethanol. The protective effect of NKA(4-10) was dose-dependent. Arg-NKB, the water soluble derivative of NKB, was less effective than NKA or NKA(4-10) while [Me-Phe7]NKB, substance P (SP) and SP-methyl-ester were inactive. The NKA(4-10) antilesion effect was reversed by pretreatment with N-ethyl-maleimide, suggesting a possible involvement of sulphydryls in its action. Among the nonmammalian tachykinins, kassinin significantly reduced ethanol-induced lesions while eledoisin and physalaemin at equivalent molar doses were inactive. These results provide, for the first time, evidence that tachykinins and their derivatives exert gastroprotective activity toward ethanol-induced haemorrhagic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved.

Animals↗
PubMedDate not supplied

A potent and selective agonist for NK-2 tachykinin receptor.

Replacement of the glycine in position 8 of the C-terminal heptapeptide NKA(4-10) with beta-alanine give rise to a potent and selective agonist for the NK-2 tachykinin receptor. The affinity of [beta-Ala8]-NKA(4-10) to the NK-2 receptor is enhanced by almost one order of magnitude as compared to NKA(4-10), while affinity decreases at about the same extent at NK-1 and NK-3 receptors, respectively. Synthesis and biological activities of a series of NKA(4-10) analogues systematically replaced in each position with beta-alanine are also reported.

Alanine↗
PubMedDate not supplied

Synthesis and biological activity of NK-2 selective tachykinin antagonists containing D-tryptophan.

By introducing D-Trp in position 6 and 8 along with pyroglutamic acid (Pyr) in position 4 or Nle in position 10 of NKA(4-10) we have obtained selective although weak NK-2 tachykinin receptor antagonists. Similar substitutions, previously reported on the sequence of SP, gave rise to nonselective antagonists presumably for the limited selectivity of the agonist used as template. Further modifications like the addition of a third D-Trp in position 9 gave rise to more potent but less selective antagonists, thus showing that each amino acid substitution can dramatically affect selectivity.

Amino Acid Sequence↗