1. Substance P (SP) infusions were given close I.A. to the feline small intestine in vivo in a dose that produced plasma concentrations of 1-5 /AM. This infusion regularly evoked a net fluid secretion measured with a gravimetric technique. Concomitantly, the release into blood of vasoactive intestinal polypeptide (VIP), a putative neurotransmitter of the enteric nervous system, increased. 2. The SP-induced fluid secretion was blocked by tetrodotoxin (7 ,ug close I.A.), a blocker of fast sodium channels in excitable tissues, and hexamethonium (10 mg (kg body wt)-', i.v.), a nicotinic receptor antagonist, suggesting that the SP effect was mediated by the enteric nervous system. In line with this it was shown that the SP-evoked release of VIP was also significantly diminished by hexamethonium. secretion caused by SP, indicating that the effects of SP were not due to the actions of prostaglandins or histamine. 5. It is proposed that SP activates a nervous reflex arch that we have shown to be activated by various luminal stimuli, including cholera toxin. The proposed reflex is made up of at least three neurons: an afferent neuron going from the mucosa to the myenteric plexus, a cholinergic interneuron and a VIP-ergic neuron from the submucosal plexus controlling the enterocytes. Met-enkephalin and the sympathetic nerves decrease the fluid secretion by pre-or postsynaptic inhibition of reflex nervous activity.We have previously shown in cat and rat experiments that the fluid secretion evoked by placing cholera toxin in the intestinal lumen or by exposing the intestinal serosa to hydrochloric acid is to a large extent mediated via an activation of reflexes in the enteric nervous system
The rate of net water uptake from the feline small intestine has been investigated during control conditions, during graded infusions of the vasodilator drug isopropylnoradrenaline, and during electrical stimulation of the regional sympathetic nerve fibres to the gut. Net water absorption rate was largely unaffected by intestinal vasodilatation. The fraction of the absorbate transported via the lymphatics remained also constrant at 20-40% of the total absorption regardless of blood flow rate. Stimulating the sympathetic nerve fibres to the small intestine increased, however, net water absorption rate. The increase was particularly pronounced when blood pressure was kept constant during the period of stimulation. The absorption rate was on an average almost doubled at a stimulation frequency of 8 Hz during constant pressure conditions. The mechanism(s) explaining this nervous control of water absorption are tentatively discussed.
Eighteen hours after intragastric inoculation Salmonella typhimurium elicited a net fluid secretion in the jejunum and ileum of rats. The mechanisms behind the secretory response were analysed in vivo. Extrinsic denervation of the experimental intestinal segments had no effect. The nerve-blocking agents hexamethonium (i.v.) and lidocaine (serosally applied) blocked the secretion but atropine had no effect. It was demonstrated that the bacteria were invasive by culturing from the intestinal wall. The presence of inflammatory reactions was supported by the facts that i.v. indomethacin blocked the secretory response and that there was an increased capillary leakage of albumin-bound Evans Blue into the interstitium of the intestinal mucosa. There was also a secretory response upon inoculation of the jejunal and ileal segments by cell-free supernatants of broth where bacteria had been cultured for 24 h and thereafter lysed. This response was, however, blocked by i.v. atropine, which had no effect on the secretion elicited by living bacteria. We could show no presence of E. coli LT, ST or cholera toxin in the cell-free supernatant by means of ELISA-tests. We therefore conclude that (1) S. typhimurium R5 invaded the rat jejunal and ileal mucosa, thereby creating an inflammatory response which in turn activated a nerve reflex(es) within the ENS leading to a net fluid secretion; (2) the presence of prostaglandins was needed for activating the reflex(es); (3) the reflex(es) contained a nicotinergic transmission; (4) enterotoxin was of no importance for the secretory response in the model used.
We have analysed tissue cyclic 3'5'-adenosine monophosphate (cAMP) concentration in different fractions of the cat's small intestinal mucosa during secretion elicited in vivo by four different secretagogues: cholera toxin (administered intraluminally), vasoactive intestinal polypeptide (VIP; given i.a.), arachidonic acid (AA; administered intraluminally) and 5-hydroxytryptamine (5-HT; given i.a.). Cholera toxin was found to increase cAMP concentration in the villi but not in the crypts. The VIP, AA and 5-HT did not influence tissue cAMP concentration despite a profuse net fluid secretion. Hexamethonium inhibited secretion elicited by cholera toxin and AA but did not significantly influence tissue cAMP concentration. There is strong evidence for the view that villus and crypt regions of the small intestinal mucosa have different functions, secretion taking place in the crypts and absorption in the villi. However, the lack of cAMP increase in the crypts reported in this study suggests that cholera toxin in this model does not reach the crypts. The results are not in agreement with a role for cAMP in mediating secretion from the crypts, but are compatible with a role of cAMP in inhibiting absorption in the villi. It is suggested that the observed fluid secretion from the crypts elicited by cholera toxin, AA and 5-HT is to a major part mediated by intramural enteric reflexes.
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