SUMMARY1. The sacral parasympathetic outflow to the large intestine of the cat was studied by monitoring simultaneously intestinal motility and the efferent firing in postganglionic fibres on the serosal surface of the mid-distal colon.2. Increases in efferent firing were noted during the occurrence of spontaneous propulsive activity (tonic pressure waves) or segmental contractions (slow rhythmic pressure waves). The neural discharge was not altered by transaction of the lumbar sympathetic innervation to the colon but was blocked by interruption of the sacral parasympathetic outflow.3. Electrical stimulation of pelvic nerve afferents arising in the colon or distension of the colon or rectum evoked reflex increases in efferent firing and sustained propulsive contractions that were associated with defaecation. Both responses were abolished by transaction of the pelvic nerves or sacral dorsal roots.4. Electrical stimulation of colonic afferent fibres also evoked synchronous reflex discharges in colonic efferents at latencies ranging from 180 to 300 msec. The discharges were enhanced during propulsive contractions, abolished by transaction of the pelvic nerves but not altered by transaction of the lumbar sympathetic nerves.5. Sacral reflexes were present in cats with intact spinal cord and in chronic spinal animals transactionn at T10-T12). The reflexes recovered within minutes to several hours after acute transaction of the spinal cord.6. Electrophysiological measurements indicated that the sacral reflexes to the large intestine were mediated by non-myelinated afferent and preganglionic efferent fibres. The central delay for the reflex was estimated to be 45-60 msec.7. It is concluded that the sacral parasympathetic reflexes to the large intestine are mediated via a spinal pathway and have an essential role in the initiation of propulsive activity during defaecation.

SUMMARY1. The origin of the lumbar sympathetic inhibitory outflow to the large intestine was studied by recording simultaneously changes in colonic motility and efferent firing in the lumbar colonic nerves (l.c.n.) following lesions at various levels of the neuraxis.2. Multiunit recordings from the l.c.n. usually consisted of irregular grouped discharges which were unrelated to spontaneous colonic contractions or to respiratory or cardiac cycles. The firing was depressed by the administration of ganglionic blocking agents or by decentralization of the inferior mesenteric ganglion, indicating that it was post-ganglionic and primarily central in origin.3. In the majority of experiments colonic motility and l.c.n. firing were not altered by transaction of the cervical (C2C3) or thoracic (T10-T 13) spinal cord. However, in these acute spinal animals destruction of the lumbar ventral roots or the lumbar spinal cord markedly enhanced colonic motility and depressed l.c.n. firing. These findings indicate supraspinal mechanisms are not essential for the generation of the lumbar inhibitory outflow to the colon.4. Transection of the l.c.n. enhanced colonic motility in animals with an intact neuraxis, in acute spinal animals and in animals where the thoracolumbar sympathetic outflow was blocked. It is concluded that peripheral ganglionic as well as spinal pathways can sustain an inhibitory input to the colon. 5. L.c.n. firing was enhanced by stretching or pinching the proximal colon or small intestine or by electrical stimulation of intestinal afferent fibres (M and C fibres) in the l.c.n. and mesenteric branches of the splanchnic nerves. The reflexes occurred via spinal pathways and were blocked by transaction of the lumbar dorsal roots. Spontaneous firing in the l.c.n. was also generated by isolated segments of the lumbar spinal cord; however, this firing occurred independently of traditional reflex pathways since it was unaffected by transaction of the lumbar dorsal roots. It is concluded that the spontaneous firing must be generated via ventral root afferent pathways or via endogenous oscillator circuits in the lumbar spinal cord.

1 The action of the lumbar sympathetic nerves to cat colon was studied in vitro using isolated muscle strips with attached lumbar colonic nerves (LCN) orientated in the axis of circular muscle layer. Electrical stimulation of LCN caused frequency-dependent increases in resting tension and in amplitude of spontaneous contractions. Contractile responses were abolished by tetrodotoxin (31M) and by guanethidine (30 JAM), indicating that they were neurogenic, involving the release of neurotransmitter from sympathetic fibres.2 Propranolol (I-9 J1M), a B-adrenoceptor antagonist, caused a concentration-dependent potentiation of LCN-evoked contractile responses. Propranolol (3 JAM) potentiated contractile responses to exogenously applied noradrenaline but not to phenylephrine.3 Phentolamine (1-9 JAM), an a-adrenoceptor antagonist, and prazosin (1-9 pM), an xl-adrenoceptor antagonist, caused a concentration-dependent reduction of amplitude but did not abolish LCN-evoked contractile responses. Prazosin (3 AM) or phentolamine (3 jaM) antagonized contractile responses to noradrenaline and phenylephrine.4 Desensitization of purinoceptors with the P2x-receptor agonist, a,j3-methylene ATP, caused a decrease in amplitude of LCN-evoked contractile responses and abolished contractile responses to ATP. In muscle strips where xl-adrenoceptors were blocked with prazosin (3 JAM) and P2-purinoceptors were desensitized with a,-methylene ATP, the amplitude of contractile responses was reduced by 82-100%.5 The P2X-purinoceptor antagonists, arylazido amino propyl adenosine triphosphate (ANAPP3) and suramin, affected LCN-evoked contractile responses. ANAPP3 (50-100 AIM) caused a concentrationdependent reduction in the amplitude of contractile response. Suramin (100 JiM) caused a small reduction in amplitude of contractile responses but potentiated their amplitude at a concentration of 500 JAM.6 ANAPP3 (100 AM) irreversibly inhibited contractions to X,P-methylene ATP or ATP. Suramin (100-500 JiM) inhibited contractions to ax,P-methylene ATP (0.5-1IJM) or low concentrations of ATP (10-50 AM) but potentiated contractions at higher concentrations. ANAPP3 (100 JiM) and suramin (100, 500 JAM) had no affect on contractile responses to noradrenaline. 7 Clonidine (0.05-1 JAM), a selective 'X2-adrenoceptor agonist, caused a concentration-dependent reduction in amplitude of LCN-evoked contractile responses, at 10 Hz, while yohimbine (0.1-1 JAM), a selective a2-adrenoceptor antagonist, increased them. At 1 JAM, both compounds affected LCN-evoked contractions at all frequencies. This suggests that prejunctional M2-receptors are involved in autoinhibition at sympathetic terminals. 8 In summary, LCN-evoked contractile responses involve the corelease of noradrenaline and ATP or a related purine nucleotide from sympathetic fibres. It is likely that the neurogenic responses are mediated through excitatory postjunctional ax-adrenoceptors, excitatory suramin-sensitive and suramin-insensitive P2X-purinoceptors and inhibitory ,-adrenoceptors. Also, autoinhibitor...

SUMMARY1. Electrophysiological techniques were used to study the sacral parasympathetic pathway to the colon of the cat.2. Electrical stimulation of the sacral ventral roots or the pelvic nerve elicited contractions of the colon and firing in nerve filaments on the serosal surface of the colon. Both responses were markedly reduced by the administration of ganglionic blocking agents. It is concluded that sacral preganglionic fibres to the colon make synaptic contacts with extramural ganglion cells. These cells were identified histologically in small ganglia on the serosal surface of the distal colon and rectum.3. Transmission in extramural colonic ganglia was cholinergic and mediated by nicotinic receptors. Colonic ganglia did not exhibit large recruiting responses during repetitive (1-4 c/s) preganglionic nerve stimulation or an adrenergic inhibitory mechanism, both of which have been identified in bladder parasympathetic ganglia. It is concluded that colonic ganglia unlike bladder ganglia function primarily as simple relay stations and have little potential for modulating the neural activity arising in the central nervous system. 4. The preganglionic input to colonic ganglia was mediated by C fibres with maximal conduction velocities ranging from 05 to 1P4 m/sec. Bladder ganglia, on the other hand, received a preganglionic input composed of B fibres with maximal conduction velocities ranging from 8 to 10 m/sec. The possible physiological significance of different types of preganglionic fibres in the sacral outflow is discussed.

The actions of NO synthase inhibitors and indomethacin, a cyclooxygenase inhibitor, on the nonadrenergic noncholinergic (NANC) mechanical responses of cat distal colon were studied in vitro using muscle strips orientated in the axis of the longitudinal muscle layer with pelvic nerves attached. Electrical field stimulation (EFS) or pelvic nerve stimulation (PNS) caused inhibition of spontaneous contractions followed by off-contractions. Indomethacin (10-30 microM) caused concentration-dependent reductions in amplitude and duration of EFS- and PNS-evoked off-contractions but not latency. The NO synthase inhibitors, N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) (each at 100 microM) significantly reduced latency, amplitude, and duration of off-contractions evoked by EFS and PNS. This inhibition was partially reversed by L-arginine (120 microM) but not by D-arginine. Incubation of colonic strips with alpha-chymotrypsin (2 U/ml) decreased latency, amplitude, and duration of NANC off-contractions. L-NNA reduced amplitude, duration, and latency of off-contractions in preparations pretreated with alpha-chymotrypsin. Hydroquinone (10-30 microM), a generator of superoxide anions, caused significant depression of amplitude, duration, and latency of off-contractions which was completely reversed by superoxide dismutase (200 U/ml). These data suggest that the components of NANC off-contractions evoked by EFS and PNS involve peptides, NO, and prostaglandins.