Mechanisms of action of neurotensin on motility of canine gastric corpus in vitro

Abstract

Increasing concentrations of neurotensin produced a biphasic contractile response, inhibition followed by excitation, when added to full-thickness circular strips of canine gastric corpus muscle cut in a circular orientation and incubated at 37.degree. C in vitro. The inhibitory response (mean effective concentration (EC50) 7 .times. 10-9 M) was not altered by addition of concentrations of tetrodotoxin or scorpion venom sufficient to block field-stimulated neural responses nor by any other antagonist tested. It would appear that inhibition is due to an excitation of the smooth muscle receptor. The excitatory response (EC50 4 .times. 10-7 M) was only present in full-thickness strips, i.e., was absent in strips of circular muscle, and was reduced by mepyramine or histamine tachyphylaxis. Pretreatment with disodium cromoglycate or repeated doses of 48/80 to extinction of the response completely eliminated the excitatory response as did repeated doses of substance P to tachyphylaxis. Since 48/80 and substance P have been shown to degranulate mast cells and disodium cromoglycate to stabilize mast cell membranes, neurotensin would appear to produce excitation by releasing histamine and other material from mast cells. In contrast to in vivo studies, where two classes of receptors producing inhibition were found, i.e., a high-affinity receptor on adrenergic nerves and a lower affinity receptor on smooth muscles, in vitro there appears to be only 1 class of receptor producing inhibition on the smooth muscle itself as no neural receptors were found. The neurotensin receptor responsible for excitation appeared to be on mast cells. The action of neurotensin thus depends upon the locus and the affinity of the receptor and the presence of the receptor on the method of study, i.e., in vivo vs. in vitro.