Biomedical subjects

L Somaini

Publications and source records attributed to L Somaini.

5 recordsLinked to original sources

PubMed2000

Glutamate receptors of the AMPA type modulate neurotransmitter release and peristalsis in the guinea-pig isolated colon.

To assess the role of AMPA and kainate receptors in modulating neurotransmitter release from the myenteric plexus, the effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on endogenous acetylcholine (ACh) and noradrenaline (NA) overflow from the guinea-pig isolated colon was studied. AMPA inhibited spontaneous ACh overflow and increased electrically-evoked NA overflow. Kainic acid did not influence both ACh and NA overflow. AMPA-mediated effects on ACh and NA overflow were significantly reduced by the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, CNQX. The inhibitory effect of AMPA on ACh overflow could be due, at least in part, to the AMPA-induced NA overflow as it was greatly reduced after adrenoceptor blockade and virtually abolished in sympathetically-denervated animals. The possible functional significance of these findings was studied by measuring the efficiency of the peristaltic reflex in the presence of the different agonists. The efficiency of peristalsis was enhanced by AMPA, whereas it was not modified by kainic acid. In conclusion, AMPA receptors, but not kainate receptors, may play a role in the modulation of ACh and NA release and of peristalsis in the guinea-pig colon.

Acetylcholine↗

PubMed1999

Modulation of enteric cholinergic neurons by hetero- and autoreceptors: cooperation among inhibitory inputs.

In the guinea-pig colon, acetylcholine (ACh) release from intrinsic cholinergic motor neurons is inhibited by adrenoceptors, opioid and muscarinic receptors. Chronic sympathetic denervation resulted in supersensitivity to the inhibitory effect of DAMGO (mu-opioid agonist) on ACh release and on the peristaltic reflex. After chronic treatment with naltrexone (NTX) supersensitivity to DAMGO and subsensitivity to UK14,304 (alpha2-adrenoceptor agonist) developed for both functional parameters. The facilitatory effect of scopolamine on ACh release remained unchanged after chronic NTX treatment, whereas it was potentiated after chronic sympathetic denervation. These data suggest the existence of a functional interaction between different inhibitory pathways modulating cholinergic motor neurons in the guinea-pig colon. Namely, chronic manipulation of an inhibitory pathway may entail adaptive sensitivity changes in another inhibitory pathway so that homeostasis can be maintained.

Acetylcholine↗

PubMed1997

Acetylcholine detection by a modified HPLC-ED method improves the assessment of cholinergic function in the myenteric plexus of the guinea-pig colon.

Because of the low basal output, measurement of acetylcholine (ACh) release from enteric neurons usually requires cholinesterase inhibition, a condition which is known to interfere with feed-back mechanisms regulating ACh release. In this study, we resorted to a highly sensitive HPLC-ED method to determine the minimum requirement of physostigmine to achieve reliable quantitation of spontaneous endogenous ACh overflow from the guinea-pig isolated colon. Furthermore, in order to assess the degree of interference by physostigmine with cholinergic function, we assessed the effect of scopolamine and oxotremorine (in the presence of physostigmine) on spontaneous ACH overflow (to detect the presence of autoreceptors) and also measured the efficiency of the peristaltic reflex with different physostigmine concentrations. Spontaneous endogenous ACh overflow was detectable only with physostigmine concentrations > or = 10 nM. ACh overflow increased with increasing physostigmine concentrations (10 nM-10 microM range). Scopolamine significantly enhanced the facilitatory effect of physostigmine concentrations > or = 10 nM; conversely, oxotremorine inhibited ACh overflow. Peristaltic efficiency was not significantly affected by physostigmine concentrations < or = 300 nM. In conclusion, this modified HPLC-ED method allows ACh detection with minimal physostigmine concentrations (10-30 nM), which do not interfere with peristaltic activity, do not saturate autoreceptor feed-back mechanisms and therefore improve the assessment of cholinergic function in colonic enteric neurons.

Acetylcholine↗

PubMed1997

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon.

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 microM) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M1-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11 -dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M2-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC50 values: 131.74 (18.19-953.96), 101.62 (58.83-175.60), 150 (60-330), 30 (5-170) nM, respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1- and M3-selective antagonist) had no significant effect up to 100 microM. 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC50 value of 0.67 (0.30-1.51) microM. The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 microM tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.

Acetylcholine↗

PubMed1995

Tonic modulation of neurotransmitter release in the guinea-pig myenteric plexus: effect of mu and kappa opioid receptor blockade and of chronic sympathetic denervation.

We have studied the effects of mu- and kappa-opioid receptor blockade on endogenous acetylcholine and noradrenaline overflow from the myenteric plexus of the guinea-pig isolated colon. Cyprodime (putative mu-selective antagonist) and nor-binaltorphimine (kappa-selective antagonist) had a concentration-dependent facilitatory effect on both acetylcholine and noradrenaline overflow. Moreover, in colonic specimens obtained from sympathetically denervated animals, the effect of opioid antagonists on acetylcholine overflow was significantly higher with respect to normal preparations. Evidence is thus given in favour of an involvement of mu- and kappa-opioid receptor pathways in the tonic modulation of neurotransmitter release at the colonic level. Enhanced sensitivity to the effect of mu and kappa antagonists after chronic sympathetic denervation is strongly suggestive for the existence of a functional link between opioid and adrenergic pathways in this model.

Acetylcholine↗