Three gaseous neurotransmitters, nitric oxide, carbon monoxide, and hydrogen sulphide, are involved in the neurogenic relaxation responses of the porcine internal anal sphincter
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The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS.
Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems.
Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist atropine (1 µM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 µM). Contractile responses were also reduced (by 45% at 5 Hz, P ? 0.01) following desensitisation of purinergic receptors with a,ß,methylene-ATP (10µM). In the presence of guanethidine, atropine and a,ß,methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor indomethacin (5 µM), the vasoactive intestinal polypeptide receptor antagonist [D-p-Cl-Phe6,Leu17]-vasoactive intestinal peptide, (PheLeu-VIP; 100 nM), or the purinoceptor antagonists 8- phenyltheophyline (P1 receptors) or suramin (P2 receptors). However relaxation responses were reduced by L-NNA (100 µM) an inhibitor of nitric oxide (NO) synthesis (40-50% reduction), zinc protoprophyrin IX (10 µM) an inhibitor of carbon monoxide (CO) synthesis (20-40% reduction) and also propargylglycine (30 µM) and aminooxyacetic acid (30 µM), inhibitors of hydrogen sulphide (H2S) synthesis (15-20% reduction).
Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst three gases mediate relaxation responses to EFS, with the combined contributions being NO>CO>H2S.
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