Effect of substance P and related neurokinins on gastric acid secretion

Substance P and a series of related neurokinins having various degrees of selectivity for tachykinin receptors have been studied for their effects on gastric acid secretion both "in vitro" and "in vivo". In the isolated gastric fundus from immature rats, substance P, the C-terminal heptapeptide of neurokinin A, NKA (4-10), [Arg]NKB and two synthetic analogues of NKA (4-10), namely, [beta-Ala8]NKA (4-10) and [Ala5]NKA (4-10) (compounds marked Men 10210 and Men 10209, respectively) had no effect on spontaneous secretion but enhanced the secretory response to histamine. All the different neurokinins were effective in the range of concentrations 10(-7) - 10(-6) M. In the conscious cat with gastric fistula, substance P dose-dependently increased basal acid secretion, whereas Men 10210 was absolutely ineffective. Men 10209 caused a slight increase in acid output which, however, was only 10% of that induced by dimaprit or pentagastrin. The secretory effect of dimaprit and pentagastrin was not affected by the different neurokinins, conversely the response to 2-Deoxy-D-glucose was slightly reduced by Men 10210 (10 nmol/kg/h). The above data suggest that the natural and synthetic neurokinins studied have negligible effects on gastric acid secretion, thus the gastro-protective effect observed in some experimental conditions is unlikely to be related to an antisecretory effect of these compounds.