Smooth muscle, neurons and interstitial cells of guinea pig ileum: are there tachykinin neurokinin 1 receptor subtypes?
Binding and autoradiographic studies were carried out in guinea pig ileum to examine neurokinin (NK) 1 receptor location and subtypes using the NK-1-selective radioligand [(125)I]Bolton-Hunter[Sar(9),Met(O(2))(11)]SP. Two membrane preparations were made: (1) longitudinal muscle containing the myenteric plexus and (2) circular muscle containing the interstitial cells of Cajal. In saturation binding studies, the K(D) was estimated as 1.3 and 1.0 nmol/l in each preparation, respectively. In competition binding, the rank order of potency was similar in both membrane preparations: SR140333 approximately CP99994 > or = [Sar(9),Met(O(2))(11)]SP approximately physalaemin approximately CP96345 (pIC(50) 9.5-8.7) >> neuropeptide gamma > or = septide (pIC(50) 7.8-7.4). Similarly, scyliorhinin I displayed equal affinity in both preparations, although binding was at two sites, of high affinity (pIC(50) 9.1, 30%) and low affinity (pIC(50) 7.2-6.6, 70%). The only competitor to bind differently in the two muscle preparations was scyliorhinin II, which bound to one site with low potency in the circular muscle (pIC(50) 6.9) but to high-affinity (pIC(50) 9.0, 17%) and low-affinity (pIC(50) 6.7, 83%) sites in the longitudinal muscle. In autoradiographic studies, dense specific binding was associated with the myenteric plexus and the inner circular muscle containing the interstitial cells of Cajal, with minimal specific binding to longitudinal and circular smooth muscle. These results suggest that the NK-1 receptor on the interstitial cells and the myenteric plexus is similar. The apparently low numbers of binding sites on intestinal smooth muscle may be due to a low expression of the NK-1 receptor. Alternatively, the radioligand may not recognize the guinea pig ileum muscle NK-1 receptors due to possible minor differences in their sequence or glycosylation.
Department of Physiology and Pharmacology, University of New South Wales, Sydney, NSW, Australia. M.Matuszek@mackillop.acu.edu.au
Maria A
MA
Matuszek
Elizabeth
E
Burcher
D000818:Animals; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009130:Muscle, Smooth / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000145:classification* / Q000378:metabolism*
D018040:Receptors, Neurokinin-1