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Neuromuscular function in the normal and inflamed colon. An experimental study in rat

Doktorsavhandling
Författare Lars Börjesson
Datum för examination 2000-12-14
ISBN 91-628-4436-9
Förlagsort Göteborg
Publiceringsår 2000
Publicerad vid Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi
Språk en
Ämnesord ATP; dextran sulphate sodium; DMPP; enteric nervous system; McN-A-343; nitric oxide; non-adrenergic; rat; second messenger; smooth muscle; VIP
Ämneskategorier Gastroenterologi

Sammanfattning

Neuromuscular function of the longitudinal muscle layer of distal colon was investigated in segments from normal rats and from rats with colitis induced by dextran sulphate sodium (DSS) at 3% for 3 or 7 days or 5% for 7 days. The study was performed in vitro, on spontaneous tone, or after precontraction. Guanethedine was present to block noradrenergic neurotransmission.Intrinsic nerves were activated by DMPP, an agonist at ganglionic, nicotinic receptors, K+, or McN-A-343, an agonist at preferentially muscarinic, neuronal receptors. The pharmacological analysis of the neurogenic response to the respective compound revealed that DMPP and K+ elicited relaxations being dependent on purinergic and nitrergic neurotransmission, and possibly also on vasoactive intestinal peptide (VIP). In contrast, the relaxation to McN-A-343 was seemingly dependent solely on ATP. While the response to K+ utilized the cGMP and the cAMP transduction systems for relaxation, that to McN-A-343 was independent of these two intracellular pathways. DSS induced dose-dependent inflammation in the distal colon. Tissue weight, optimal preload, response to carbachol, tone and phasic contractile activity was increased in segments from rats treated with 5% DSS. The adaptive relaxatory response to preload was abolished in DSS treated animals, possibly due to impaired nitrergic neurotransmission. In animals treated with 5% DSS, some results indicate prevailing inhibition of the colon muscle mediated by (non-neurogenic) nitric oxide, which could be an effect of the inflammation.It is concluded that non-adrenerig, inhibitory neurotransmission in rat distal colon depend on ATP, nitric oxide and VIP and that activation of muscarinic, neuronal receptors may selectivly release ATP. DSS colitis induce myogenic, neuronal, and possibly also paracrine alterations of the neuromuscular function in rat distal colon

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