STIMULATION OF LUMBAR SYMPATHETIC-NERVES EVOKES CONTRACTIONS OF CAT COLON CIRCULAR MUSCLE MEDIATED BY ATP AND NORADRENALINE

1 The action of the lumbar sympathetic nerves to cat colon was studied in vitro using isolated muscle strips with attached lumbar colonic ne rves (LCN) orientated in the axis of circular muscle layer. Electrical stimulation of LCN caused frequency-dependent increases in resting te nsion and in amplitude of spontaneous contractions. Contractile respon ses were abolished by tetrodotoxin (3 muM) and by guanethidine (30 muM ), indicating that they were neurogenic, involving the release of neur otransmitter from sympathetic fibres. 2 Propranolol (1-9 muM), a beta- adrenoceptor antagonist, caused a concentration-dependent potentiation of LCN-evoked contractile response. Propranolol (3 muM) potentiated c ontractile responses to exogenously applied noradrenaline but not to p henylephrine. 3 Phentolamine (1-9 mum), an alpha-adrenoceptor antagoni st, and prazosin (1-9 muM), an alpha1-adrenoceptor antagonist, caused a concentration-dependent reduction of amplitude but did not abolish L CN-evoked contractile responses. Prazosin (3 muM) or phentolamine (3 m uM) antagonized contractile responses to noradrenaline and phenylephri ne. 4 Desensitization of purinoceptors with the P2x-receptor agonist, alpha,beta-methylene ATP, caused a decrease in amplitude of LCN-evoked contractile responses and abolished contractile responses to ATP. In muscle strips where alpha1-adrenoceptors were blocked with prazosin (3 muM) and P2-purinoceptors were desensitized with alpha,beta-methylene ATP, the amplitude of contractile responses was reduced by 82-100%. 5 The P2X-purinoceptor antagonists, arylazido amino propyl adenosine tr iphosphate (ANAPP3) and suramin, affected LCN-evoked contractile respo nses. ANAPP3 (50-100 muM) caused a concentration-dependent reduction i n the amplitude of contractile response. Suramin (100 muM) caused a sm all reduction in amplitude of contractile responses but potentiated th eir amplitude at a concentration of 500 muM. 6 ANAPP3 (100 muM) irreve rsibly inhibited contractions to alpha,beta-methylene ATP or ATP. Sura min (100-500 muM) inhibited contractions to alpha,beta-methylene ATP ( 0.5-1 muM) or low concentrations of ATP (10-50 muM) but potentiated co ntractions at higher concentrations. ANAPP3 (100 muM) and suramin (100 , 500 muM) had no affect on contractile responses to noradrenaline. 7 Clonidine (0.05-1 muM), a selective alpha2-adrenoceptor agonist, cause d a concentration-dependent reduction in amplitude of LCN-evoked contr actile responses, at 10 Hz, while yohimbine (0.1-1 muM), a selective a lpha2-adrenoceptor antagonist, increased them. At 1 muM, both compound s affected LCN-evoked contractions at all frequencies. This suggests t hat prejunctional alpha2-receptors are involved in autoinhibition at s ympathetic terminals. 8 In summary, LCN-evoked contractile responses i nvolve the corelease of noradrenaline and ATP or a related purine nucl eotide from sympathetic fibres. It is likely that the neurogenic respo nses are mediated through excitatory postjunctional alpha1-adrenocepto rs, excitatory suramin-sensitive and suramin-insensitive P2X-purinocep tors and inhibitory beta-adrenoceptors. Also, autoinhibitory prejuncti onal alpha2-adrenoceptors regulate the LCN excitatory pathway to cat c olon circular muscle.