AJP - Gastrointestinal and Liver Physiology, Vol 249, Issue 4 533-G538, Copyright © 1985 by American Physiological Society
Receptors for mammalian tachykinins on isolated intestinal smooth muscle cells
J. C. Souquet, J. R. Grider, K. N. Bitar and G. M. Makhlouf
The existence of receptors for three mammalian tachykinins, substance P
(SP), substance K (SK), and neuromedin K (NK), was examined in smooth
muscle cells, isolated separately from the longitudinal and circular muscle
layers of guinea pig ileum. Tachykinin receptors capable of mediating
contraction were present in muscle cells from both layers. The receptors
were selectively blocked by the tachykinin antagonist [D-Pro2,
D-Trp7,9]substance P but not by muscarinic, gastrin/cholecystokinin, or
opiate antagonists (0.3 nM atropine, 1 mM proglumide, and 0.3 nM naloxone,
respectively). The rank order of potency of tachykinins in causing
contraction, NK greater than SP greater than SK, was similar in both muscle
cell types. The results obtained in isolated muscle cells were closely
paralleled by results obtained in intact muscle strips; the main difference
was the greater sensitivity of isolated cells to tachykinin agonists
(250-fold) and antagonist (210-fold). The inhibitory dissociation constant
(Ki) of [D-Pro2, D-Trp7,9]substance P estimated from the displacement of
dose-response curves (muscle cells) or from Schild plots (muscle strips)
differed minimally or not at all, when either SP or SK was used as agonist,
consistent with interaction of the two peptides with the same receptor
subtype. The notion of a single receptor subtype in ileal muscle cells of
the guinea pig was further supported by the occurrence of complete
cross-desensitization between SP and SK in muscle strips.
