Subtypes and excitation-contraction coupling mechanisms for neurokinin receptors in smooth muscle of the guinea-pig Taenia caeci

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1991-08, Vol.344 (2), p.225-234
• Main Authors: HALL, J. M, MORTON, I. K. M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Carbachol - pharmacology; contraction; Fundamental and applied biological sciences. Psychology; Guinea Pigs; In Vitro Techniques; Intestine. Mesentery; Intestines - drug effects; Intestines - physiology; Ion Channels - physiology; Lithium - pharmacology; mechanisms; mediation; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; neurokinin; Phosphatidylinositols - metabolism; Potassium - pharmacology; receptors; Receptors, Neurokinin-2; Receptors, Neurotransmitter - analysis; Receptors, Neurotransmitter - physiology; Rubidium Radioisotopes - metabolism; smooth muscle; subtypes; tachykinin; Tachykinins - pharmacology; Vertebrates: digestive system
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00167223

This study investigated the subtype and coupling mechanisms mediating the direct contractile response to tachykinins in the guinea-pig Taenia caeci preparation in vitro. Coupling of neurokinin receptors was compared throughout with coupling of muscarinic receptors. The smooth muscle neurokinin receptors seem to be predominantly of the NK-1 subtype. Thus, the relative activities of the common naturally-occurring tachykinins fell within one order of magnitude, and the selective NK-1 receptor agonist substance P methyl ester was high in activity (0.38 relative to substance P). Some contribution from NK-3 receptors is, however, possible in view of the appreciable activity of the selective NK-3 agonist succ-[Asp6, N-MePhe8]-SP(6-11) (senktide; activity 0.004 relative to substance P), and NK-2 or NK-3 receptors in view of the higher activity of the D-isomer of [Glp6, *Pro9]-SP(6-11) as compared to its NK-1 selective L-isomer (D/L-activity ratio 1.53). Contractile actions of tachykinins were compared with carbachol for reliance on membrane-potential dependent (electromechanical) and membrane-potential independent (pharmacomechanical) coupling mechanisms. Log concentration-response curves to carbachol and substance P in normal Krebs' medium were compared with curves obtained in a high-K+ solution where processes dependent on changes in membrane potential could play no part in excitation. In the high-K+ depolarizing solution, a concentration-related relationship was maintained, though with some diminution in the maximal additional tension generated: the maximum tension with carbachol was under both conditions greater than that with substance P. The relative effects of several tachykinins and carbachol in producing receptor-mediated changes in membrane permeability through presumed receptor-operated ion channel opening, was estimated in terms of the ability to increase 86Rb-efflux, as a marker for K+, in a high-K+ depolarizing solution. Carbachol (10 microM) consistently increased 86Rb-efflux. In contrast, no permeability increase could be detected with any tachykinin tested (substance P, eledoisin, substance P methyl ester, neurokinin A, neurokinin B, 1 or 10 microM). Tachykinins and carbachol were compared in terms of ability to increase phosphatidylinositol hydrolysis. Both substance P and carbachol showed a concentration-related increase in accumulation of total inositol phosphates; though the maximal response to carbachol was considerably greater than that to a