Effect of substance P and neurokinin A on rat parietal cell function.
In enzymatically dispersed enriched (76%) rat parietal cells we studied the effect of substance P on acid sequestration as indirectly measured by [14C]aminopyrine accumulation. Substance P (10(-8)-10(-5) M) had no effect on basal [14C]aminopyrine accumulation. Yet, the peptide reduced the response to histamine and to the postreceptor agonists forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Inhibition by substance P followed noncompetitive kinetics and reduced stimulated parietal cell function by up to 45% at 10(-5) M. The antagonist [D-Pro2, D-Trp7,9]-substance P at 10(-5) M partly reversed the inhibitory effect of substance P. Cholinergic stimulation of [14C]aminopyrine accumulation was not reduced by substance P. Neurokinin A, another tachykinin that is structurally related to substance P, was of comparable potency and efficacy in reducing [14C]aminopyrine accumulation in response to histamine, forskolin, and DBcAMP. Inhibition of forskolin- or DBcAMP-induced [14C]aminopyrine accumulation persisted in the presence of 10(-5) M ranitidine. Inhibition by substance P and neurokinin A of the response to histamine was not sensitive to pertussis toxin. Both tachykinins failed to reduce histamine- and forskolin-stimulated cAMP production. Our data suggest that substance P and neurokinin A exert a direct effect on rat parietal cells. They attenuate histamine-stimulated acid sequestration at an intracellular step that is distal to the adenylate cyclase and that does not involve pertussis toxin-sensitive GTP-binding proteins.
Department of Internal Medicine II, Technical University of Munich, Federal Republic of Germany.
W
W
Schepp
J
J
Schmidtler
C
C
Tatge
V
V
Schusdziarra
M
M
Classen
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002469:Cell Separation; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D015288:Neurokinin A / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
D000632:Aminopyrine; D005576:Colforsin; D013373:Substance P; D003994:Bucladesine; D006632:Histamine; D015288:Neurokinin A; D002217:Carbachol; D000242:Cyclic AMP