Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine.

Abstract

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

Modulation by Dietary Salt of Verapamil Disposition in Humans

“…26 Thus, one possible mechanism underlying the effect of dietary salt on drug disposition may relate to an alteration in sympathetic activity, consistent with reported links between autonomic and gastrointestinal function. [27][28][29] Another possibility is that increases in sodium or chloride concentration in the intestinal lumen serve as an initial signal for altered intestinal expression of genes encoding proteins such as CYP3A4 or P-glycoprotein.…”

Expression of NK1 receptor at the protein and mRNA level in the porcine female reproductive system

“…Interest in Substance P was resulting not only from its involvement in sensory neurotransmission, but also from its role in regulation of the blood flow, blood vessels permeability (Brunsson et al 1995) and the progress of the inflammation (Mantyh 1991). The action of neuropeptides through specific receptors directed also much of interest into this field, as receptors are natural targets for would-be drugs.…”

“…The presence of specific receptors may be deduced from the fact of the presence of nerve fibers containing the neuropeptide, as well as from the effect of the neuropeptide on the tissues (Brunsson et al 1995).…”

Stimulation by enkephalins of D-glucose absorption in rabbit ileum

“…Once again, the decrease can be attributed to a variation in the transepithelial Na + and Cl − net fluxes which are electrogenic and responsible for the short-circuit current [28]. The increase in Na + , Cl − and H 2 O absorption produced by the addition of DAGO in open circuit conditions (everted sac technique) indicates a reduction in electrogenic Cl − (and water) secretion, the consequence of which is a reduction in I sc [7,29]. The stimulatory effect of DAGO on ZI sc,glu is in accordance with the increase in D-glucose transport observed in the everted sac experiments.…”