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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

270 records · Page 15Linked to original sources
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

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

Is there a relationship between rat latent aggressiveness and susceptibility to convulsive crises?

Experiments were aimed at assessing a possible different sensitiveness to seizures in aggressive vs. nonaggressive rates. Thirty-nine muricidal rats were selected by using a sedated mouse. Six of these killer rats (K) showed electroencephalographic (EEG) spontaneous syncronous wave-and-spike discharges, 6-11 c/s. None of nonkiller animals (NK) showed a similar pattern. These 6 K were not used for the subsequent experiments. Intraperitoneal pentylentetrazole (PTZ; 10, 20, and 40 mg/kg) or bicuculline (BIC; 2 and 4 mg/kg) was given to both NK and K. K were more sensitive than NK to the epileptogenic effects of 20 mg/kg PTZ and 2 mg/kg BIC, as revealed by the significant increased number of convulsive rats and longer duration of EEG seizures. No difference in EEG or convulsant behavior was observed between K and NK after the administration of the lower dose of PTZ and the high dose of PTZ or BIC. The use of K rats as a possible new sensitive model of petit mal is discussed.

Aggression↗
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↗
PubMedDate not supplied

Response to hypogravity of normal in vitro cultured follicular cells from thyroid.

Aim of this investigation is the study of molecular modifications occurring in differentiated mammalian cells exposed to gravitational changes. The test system chosen is a well characterized clone of differentiated, normal thyroid follicular cells (FRTL5) in long-term culture. As a follow-up to our recent experiment performed during the MASER-7 sounding rocket mission, flown for European Space Agency by Swedish Space Corporation in May 1996, we evaluated FRTL5 cells responses to Thyroid Stimulating Hormone dependent cAMP production under acute hypogravity conditions obtained in a fast rotating clinostat. Following this approach, we evaluated the FRTL5 cells response to TSH under microgravity conditions in order to optimize experimental tools and strategies in preparation to, and in between real flight missions.

Animals↗
PubMedDate not supplied

Synthesis and biological activity of N-methylated analogues of neurokinin A.

Limited conformational constraints have been introduced in the sequence of the C-terminal heptapeptide NKA(4-10) by N-methylation of individual peptide bonds and the biological activities of the peptides thus obtained were evaluated on three in vitro preparations sensitive and quite selective for each of the naturally-occurring neurokinins, in order to assess the effect of N-methylation on receptor selectivity. The analogue methylated in position 7, namely [MeVal7] NKA(4-10) shows some selectivity for the NK-P receptor, while none of the tested compounds appear to be selective for the NK-A receptor.

Animals↗
PubMedDate not supplied

Autoradiographic localization of octylonium bromide binding sites in the rat gastrointestinal tract.

The anatomical localization of the binding sites of the spasmolytic drug octylonium bromide (OB) in the rat gastrointestinal tract was analyzed by use of light microscope autoradiography. The drug was visualized after in vitro incubation of frozen sections of the gastrointestinal tract with a 10 nM concentration of 14C-OB and after in vivo injection into the ascending, transverse, descending and sigmoidal portions of the colon. In vitro experiments demonstrated the specific accumulation of 14C-OB within the colonic and rectal smooth muscle. In contrast, no specific binding of the radiolabeled drug was noticeable in the stomach or in the small intestine. In vivo intracolonic injection of 14C-OB showed a significant accumulation of the drug in the colonic musculature 2 min after administration. The predominant localization of 14C-OB in the colonic and rectal musculature could explain its effectiveness in suppressing the amplitude and frequency of colonic contractions and in controlling the irritable bowel syndrome.

Animals↗