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Receptors for Gut Peptides on Smooth Muscle Cells of the Gut

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Abstract

The sections in this article are:

1 Receptors for Cholecystokinin
2 Receptors for Tachykinins
3 Receptors for Opioid Peptides
4 Receptors for Bombesins
5 Receptors for Vasoactive Intestinal Peptide
6 Receptors for Neuropeptide Y
7 Receptors for Calcitonin Gene‐Related Peptide
8 Receptors for Galanin
9 Receptors for Somatostatin
10 Receptors for Motilin
Figure 1. Figure 1.

Concentration‐response curves for contractile effects of cholecystokinin octapeptide [CCK‐OP (CCK‐8)] (closed circles), gastrin‐17 (closed squares), and acetylcholine (open circles) in isolated muscle cells from guinea pig stomach. CCK‐8 and gastrin‐17 are equipotent in gastric muscle cells. Responses in muscle cells from human stomach are identical.

From Bitar and Makhlouf 10
Figure 2. Figure 2.

Inhibition of contractile response of muscle cells isolated from gallbladder of dog by a preferential antagonist of substance P, [D‐Pro2,D‐Trp7,9]SP ([PTT]SP), and a preferential antagonist of bombesin, [D‐Arg1,D‐Pro2,D‐Trp7,9,Leu11]SP ([APTTL]SP). Differential effects of 2 antagonists are consistent with presence of separate receptors for SP and bombesin.

From Severi et al. 69
Figure 3. Figure 3.

Inhibition of specific binding of 125I‐labeled substance P by mammalian tachykinins and the substance P (SP) derivative, [D‐Pro2,D‐Trp7,9]SP, in isolated cells from longitudinal muscle layer of guinea pig small intestine. Same order of potency prevails when 125I‐labeled substance K is used as radioligand.

From Souquet et al. 72
Figure 4. Figure 4.

Concentration‐response curves for contractile effects of opioid peptides, dynorphin (DYN), Met‐enkephalin (MET‐ENK), Met‐enkephalin‐Arg6‐Phe7 (MEAP), β‐neoendorphin (β‐NEO‐E), and Leu‐enkephalin (LEU‐ENK) on smooth muscle cells isolated separately from circular and longitudinal muscle layers of guinea pig small intestine. Identical pattern of selective response in circular muscle cells is found in human intestine.

From Bitar and Makhlouf 13
Figure 5. Figure 5.

Concentration‐response curves for contractile effects of amphibian bombesin‐14 and 3 mammalian bombesins, neuromedin B, gastrin‐releasing peptide (GRP1–27), and the COOH‐terminal decapeptide of GRP (GRP18–27) on muscle cells isolated from circular muscle layer of human jejunum.

From Micheletti et al. 60
Figure 6. Figure 6.

Concentration‐response curves for relaxant effect of vasoactive intestinal peptide (VIP), alone and in combination with a threshold (open squares) and suprathreshold (open circles) concentration of isobutyl methylxanthine (IBMX).

From Bitar and Makhlouf 11


Figure 1.

Concentration‐response curves for contractile effects of cholecystokinin octapeptide [CCK‐OP (CCK‐8)] (closed circles), gastrin‐17 (closed squares), and acetylcholine (open circles) in isolated muscle cells from guinea pig stomach. CCK‐8 and gastrin‐17 are equipotent in gastric muscle cells. Responses in muscle cells from human stomach are identical.

From Bitar and Makhlouf 10


Figure 2.

Inhibition of contractile response of muscle cells isolated from gallbladder of dog by a preferential antagonist of substance P, [D‐Pro2,D‐Trp7,9]SP ([PTT]SP), and a preferential antagonist of bombesin, [D‐Arg1,D‐Pro2,D‐Trp7,9,Leu11]SP ([APTTL]SP). Differential effects of 2 antagonists are consistent with presence of separate receptors for SP and bombesin.

From Severi et al. 69


Figure 3.

Inhibition of specific binding of 125I‐labeled substance P by mammalian tachykinins and the substance P (SP) derivative, [D‐Pro2,D‐Trp7,9]SP, in isolated cells from longitudinal muscle layer of guinea pig small intestine. Same order of potency prevails when 125I‐labeled substance K is used as radioligand.

From Souquet et al. 72


Figure 4.

Concentration‐response curves for contractile effects of opioid peptides, dynorphin (DYN), Met‐enkephalin (MET‐ENK), Met‐enkephalin‐Arg6‐Phe7 (MEAP), β‐neoendorphin (β‐NEO‐E), and Leu‐enkephalin (LEU‐ENK) on smooth muscle cells isolated separately from circular and longitudinal muscle layers of guinea pig small intestine. Identical pattern of selective response in circular muscle cells is found in human intestine.

From Bitar and Makhlouf 13


Figure 5.

Concentration‐response curves for contractile effects of amphibian bombesin‐14 and 3 mammalian bombesins, neuromedin B, gastrin‐releasing peptide (GRP1–27), and the COOH‐terminal decapeptide of GRP (GRP18–27) on muscle cells isolated from circular muscle layer of human jejunum.

From Micheletti et al. 60


Figure 6.

Concentration‐response curves for relaxant effect of vasoactive intestinal peptide (VIP), alone and in combination with a threshold (open squares) and suprathreshold (open circles) concentration of isobutyl methylxanthine (IBMX).

From Bitar and Makhlouf 11
References
 1. Beaujouan, J. C., Y., Torrens, A. Viger, and J. Glowinski. A new type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative. Mol. Pharmacol. 26: 248–254, 1984.
 2. Behar, J., and P. Biancani. Effect of cholecystokinin‐octapeptide on the lower esophageal sphincter. Gastroenterology 73: 57–61, 1977.
 3. Behar, J., and P. Biancani. Pharmacologic characterization of excitatory and inhibitory cholecystokinin receptors on the cat gallbladder and sphincter of Oddi. Gastroenterology 92: 764–770, 1987.
 4. Biancani, P., C., Hillemeier, K. N. Bitar, and G. M. Makhlouf. Contraction mediated by Ca2+ influx in esophageal muscle and by Ca2+ release in the LES. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G760–G766, 1987.
 5. Biancani, P., J. H., Walsh, and J. Behar. Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation. J. Clin. Invest. 73: 963–967, 1984.
 6. Biancani, P., J. H., Walsh, and J. Behar. Vasoactive intestinal peptide: a neurotransmitter for relaxation of the rabbit internal anal sphincter. Gastroenterology 89: 867–874, 1985.
 7. Bitar, K. N., P., Bradford, J. W. Putney, and G. M. Makhlouf. Cytosolic calcium during contraction of isolated mammalian gastric muscle cells. Science Wash. DC 232: 1143–1145, 1986.
 8. Bitar, K. N., G. M., Burgess, J. W. Putney, JR., and G. M. Makhlouf. Source of activator calcium in isolated guinea pig and human gastric muscle cells. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G280–G286, 1986.
 9. Bitar, K. N., and R. T. Jensen. Binding of 125I‐VIP to isolated gastric smooth muscle cells (Abstract). Gastroenterology 84: 1107, 1983.
 10. Bitar, K. N., and G. M. Makhlouf. Receptors on smooth muscle cells: characterization by contraction and specific antagonists. Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G400–G407, 1982.
 11. Bitar, K. N., and G. M. Makhlouf. Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide. Science Wash. DC 261: 531–533, 1982.
 12. Bitar, K. N., and G. M. Makhlouf. Specific opiate receptors on isolated mammalian gastric smooth muscle cells. Nature Lond. 297: 72–74, 1982.
 13. Bitar, K. N., and G. M. Makhlouf. Selective presence of opiate receptors on intestinal circular muscle cells. Life Sci. 37: 1545–1550, 1985.
 14. Bitar, K. N., and G. M. Makhlouf. Measurement of function in isolated single smooth muscle cells. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G357–G360, 1986.
 15. Bitar, K. N., B., Saffouri, and G. M. Makhlouf. Cholinergic and peptidergic receptors on isolated human antral smooth muscle cells. Gastroenterology 82: 832–837, 1982.
 16. Buck, S. H., E., Burcher, C. W. Shults, W. Lovenberg, and T. L. O'Donohue. Novel pharmacology of substance K‐binding sites: a third type of tachykinin receptor. Science Wash. DC 226: 987–989, 1984.
 17. Burcher, E., S. H., Buck, W. Lovenberg, and T. L. O'Donohue. Characterization and autoradiographic localization of multiple tachykinin binding sites in gastrointestinal tract and bladder. J. Pharmacol. Exp. Ther. 236: 819–831, 1986.
 18. Costa, M., and J. B. Furness. The origins, pathways and terminations of neurons with VIP‐like immunoreactivity in the guinea pig small intestine. Neuroscience 8: 665–676, 1983.
 19. Costa, M., J. B., Furness, and I. J. Llewellyn‐Smith. Histochemistry of the enteric nervous system. In: Physiology of the Gastrointestinal Tract (2nd ed.), edited by L. R. Johnson. New York: Raven, 1987, vol. 1, p. 1–40.
 20. Costa, M., J. B., Furness, I. J. Llewellyn‐Smith, B. Davies, and J. Oliver. An immunohistochemical study of projections of somatostatin‐containing neurons in the guinea‐pig intestine. Neuroscience 5: 841–852, 1980.
 21. Costa, M., J. B., Furness, C. O. Pullin, and J. Bornstein. Substance P enteric neurons mediate non‐cholinergic transmission to the circular muscle of the guinea‐pig intestine. Naunyn‐Schmiedeberg's Arch. Pharmacol. 328: 446–453, 1985.
 22. Cox, K. L., T. VON, Schrenck, T. H. Moran, J. D. Gardner, and R. T. Jensen. Characterization of cholecystokinin (CCK) receptors on the smooth muscle of the sphincter of Oddi (Abstract). Gastroenterology 94: A80, 1988.
 23. Evans, B. E., M. G., Bock, K. E. Rittle, R. M. Dipardo, W. L. Whitter, D. F. Veber, P. S. Anderson, and R. M. Freidinger. Design of potent, orally effective, nonpeptidal antagonists of the peptide hormone cholecystokinin. Proc. Natl. Acad. Sci. USA 83: 4918–4922, 1986.
 24. Folkers, K., Y.‐A., Lu, and S. Rosell. Synthesis and biological activities of neurokinin α and β. Biochem. Biophys. Res. Commun. 118: 405–408, 1984.
 25. Fosbraey, P., R. L. Featherstone, and I. K. M. Morton. Comparison of potency of substance P and related peptides on [3H]‐acetylcholine release, and contractile actions, in the guinea‐pig ileum. Arch. Pharmacol. 326: 111–115, 1984.
 26. Furness, J. B., M., Costa, P. C. Emson, R. Hakanson, E. Moghimzadeh, F. Sundler, I. L. Taylor, and R. E. Chance. Distribution, pathways and reactions to drug treatment of nerves with neuropeptide Y‐ and pancreatic polypeptide‐like immunoreactivity in the guinea‐pig digestive tract. Cell Tissue Res. 234: 71–92, 1983.
 27. Goyal, R. K., S., Rattan, and S. I. Said. VIP as a possible neurotransmitter of non‐cholinergic, non‐adrenergic inhibitory neurons. Nature Lond. 288: 378–380, 1980.
 28. Grider, J. R., A., Arimura, and G. M. Makhlouf. Role of somatostatin neurons in intestinal peristalsis: facilitatory interneurons in descending pathways. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G434–G438, 1987.
 29. Grider, J. R., M. B., Cable, K. N. Bitar, S. I. Said, and G. M. Makhlouf. Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig. Gastroenterology 89: 36–42, 1985.
 30. Grider, J. R., and G. M. Makhlouf. Colonic peristaltic reflex: identification of vasoactive intestinal peptide as mediator of descending relaxation. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14): G40–G45, 1986.
 31. Grider, J. R., and G. M. Makhlouf. Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut. Gastroenterology 92: 175–180, 1987.
 32. Grider, J. R., and G. M. Makhlouf. Suppression of inhibitory neural input to colonic muscle by opioid peptides. J. Pharmacol. Exp. Ther. 243: 205–210, 1987.
 33. Grider, J. R., and G. M. Makhlouf. Prejunctional inhibition of vasoactive intestinal peptide release. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G7–G12, 1987.
 34. Grider, J. R., and G. M. Makhlouf. Role of opioid neurons in the regulation of intestinal peristalsis. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G226–G231, 1987.
 35. Grider, J. R., and G. M. Makhlouf. Contraction mediated by Ca2+ release in circular and Ca2+ influx in longitudinal intestinal muscle cells. J. Pharmacol. Exp. Ther. 244: 432–437, 1988.
 36. Grider, J. R., and G. M. Makhlouf. Differentiation of gastrin and CCK receptors on single muscle cells of the stomach, intestine, and gallbladder with selective protective ligands (Abstract). Gastroenterology 94: A156, 1988.
 37. Grider, J. R., and G. M. Makhlouf. Identification of distinct opioid receptor types on gastric muscle cells with selective protective ligands and site directed irreversible antagonists (Abstract). Gastroenterology 94: A157, 1988.
 38. Grider, J. R., and G. M. Makhlouf. The modulatory function of galanin: potentiation of VIP‐induced relaxation in isolated smooth muscle cells (Abstract). Gastroenterology 94: A157, 1988.
 39. Grider, J. R., and G. M. Makhlouf. Regulation of the ascending contraction component of the peristaltic reflex by myenteric tachykinin neurons (Abstract). Gastroenterology 94: A157, 1988.
 40. Grider, J. R., and G. M. Makhlouf. VIP: transmitter of inhibitory neurons of the gut. Ann. NY Acad. Sci. 527: 369–377, 1988.
 41. Grider, J. R., J., Rivier, and G. M. Makhlouf. Evidence for VIP as transmitter of inhibitory motor neurons: blockade of neurally‐mediated relaxation by VIP antagonists (Abstract). Gastroenterology 92: 1415, 1987.
 42. Holzer, P., and F. Lembeck. Neurally mediated contraction of ileal longitudinal muscle by substance P. Neurosci. Lett. 17: 101–105, 1980.
 43. Holzer, P., I. T., Lippe, L. Bartho, and A. Saria. Neuropeptide Y inhibits excitatory enteric neurons supplying the circular muscle of the guinea pig small intestine. Gastroenterology 92: 1944–1950, 1987.
 44. Hunter, J. C., and J. E. Maggio. A pharmacological study with substance K: evidence for multiple types of tachykinin receptors. Eur. J. Pharmacol. 105: 149–153, 1984.
 45. Itoh, N., K., Obata, N. Yanaihara, and H. Okamoto. Human preprovasoactive intestinal polypeptide contains a novel PHI‐27‐like peptide, PHMN‐27. Nature Lond. 304: 547–549, 1983.
 46. Jensen, R. T., S. W., Jones, K. Folkers, and J. D. Gardner. A synthetic peptide that is a bombesin receptor antagonist. Nature Lond. 309: 61–63, 1984.
 47. Jensen, R. T., R. B., Murphy, M. Trampota, L. H. Schneider, S. W. Jones, J. M. Howard, and J. D. Gardner. Proglumide analogues: potent cholecystokinin receptor antagonists. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G214–G220, 1985.
 48. Kakidani, H., Y., Furutani, H. Takahashi, M. Noda, Y. Morimoto, T. Hirose, M. Asai, S. Inayama, S. Nakanishi, and S. Numa. Cloning and sequence analysis of cDNA for porcine β‐neo‐endorphin/dynorphin precursor. Nature Lond. 298: 245–249, 1982.
 49. Kangawa, K., N., Minamino, A. Fukuda, and H. Matsuo. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem. Biophys. Res. Commun. 114: 533–540, 1983.
 50. Kantoh, M., T., Takahashi, T. Yamamura, Y. Ishikawa, and J. Utsunomiya. Bombesin evoked acetylcholine release from the guinea pig antrum. Life Sci. 36: 2445–2452, 1985.
 51. Laufer, R., U., Wormser, Z. Y. Friedman, C. Gilon, M. Chorev, and Z. Selinger. Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin. Proc. Natl. Acad. Sci. USA 82: 7444–7448, 1985.
 52. Leander, S., R., Ekman, R. Uddman, F. Sundler, and R. Hakanson. Neuronal cholecystokinin, gastrin‐releasing peptide, neurotensin, and β‐endorphin in the intestine of the guinea pig. Distribution and possible motor functions. Cell Tissue Res. 235: 521–531, 1984.
 53. Louie, D. S., and C. Owyang. Motilin receptors on isolated gastric smooth muscle cells. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G210–G216, 1988.
 54. Makhlouf, G. M. Enteric neuropeptides: role in neuromuscular activity of the gut. Trends Pharmacol. Sci. 6: 214–218, 1985.
 55. Makhlouf, G. M. Isolated smooth muscle cells of the gut. In: Physiology of the Gastrointestinal Tract (2nd ed.), edited by L. R. Johnson. New York: Raven, 1987, vol. 1, p. 555–569.
 56. Maton, P. N., V. E., Sutliff, Z.‐C. Zhou, S. M. Collins, J. D. Gardner, and R. T. Jensen. Characterization of receptors for calcitonin gene‐related peptide on gastric smooth muscle cells. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G789–G794, 1988.
 57. Mayer, E. A., J., Elashoff, and J. H. Walsh. Characterization of bombesin effects on canine gastric muscle. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G141–G147, 1982.
 58. Melander, T., T., Hökfelt, A. Rökaeus, J. Fahrenkrug, K. Tatemoto, and V. Mutt. Distribution of galanin‐like immunoreactivity in the gastro‐intestinal tract of several mammalian species. Cell Tissue Res. 239: 253–270, 1985.
 59. Menozzi, D., J. D., Gardner, R. T. Jensen, and P. Maton. Characteristics of gastrin receptors on gastric smooth muscle. Gastroenterology 92: 1531, 1987.
 60. Micheletti, R., J. R., Grider, and G. M. Makhlouf. Identification of bombesin receptors on isolated muscle cells from human intestine. Regul. Pept. 21: 219–226, 1988.
 61. Nawa, H., M., Doteuchi, K. Igano, K. Inouye, and S. Nakanishi. Substance K: a novel mammalian tachykinin that differs from substance P in its pharmacological profile. Life Sci. 34: 1153–1160, 1984.
 62. Nawa, H., T., Hirose, H. Takashima, S. Inayama, and S. Nakanishi. Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature Lond. 306: 32–36, 1983.
 63. Noda, M., Y., Furutani, H. Takahashi, M. Toyosato, T. Hirose, T. Inayama, S. Nakanishi, and S. Numa. Cloning and sequence analysis of cDNA for bovine adrenal preproenkephalin. Nature Lond. 295: 202–206, 1982.
 64. Paton, W. D. M., and M. A. Zar. The origin of acetylcholine released from guinea pig intestine and longitudinal muscle strips. J. Physiol. Lond. 194: 13–33, 1968.
 65. Rattan, S., and R. K. Goyal. Structure activity relationship of subtypes of cholecystokinin receptors in the cat lower esophageal sphincter. Gastroenterology 90: 94–102, 1986.
 66. Rokäeus, A. Galanin: a newly isolated biologically active neuropeptide. Trends Neurosci. 10: 158–164, 1987.
 67. Schjoldager, B., M. J., Shaw, S. P. Powers, P. F. Schmalz, J. Szurszewski, and L. J. Miller. Bovine gallbladder muscularis: source of a myogenic receptor for cholecystokinin. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G294–G299, 1988.
 68. Schmalz, P. F., K. G., Morgan, and J. H. Szurszewski. Pentagastrin potentiates nonadrenergic inhibitory neuromuscular transmission in orad stomach of the dog. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G597–G600, 1983.
 69. Severi, C., J. R., Grider, and G. M. Makhlouf. Identification of separate bombesin and substance P receptors on isolated muscle cells from canine gallbladder. J. Pharmacol. Exp. Ther. 245: 195–198, 1988.
 70. Severi, C., J. R., Grider, and G. M. Makhlouf. Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells. Life Sci. 42: 2373–2380, 1988.
 71. Severi, C., J. R., Grider, and G. M. Makhlouf. Functional gradients in muscle cells isolated from gallbladder, cystic duct, and common bile duct. Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 18): G647–G652, 1988.
 72. Souquet, J.‐C., K. N., Bitar, J. R. Grider, and G. M. Makhlouf. Receptors for substance P on isolated intestinal smooth muscle cells of the guinea pig. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G666–G672, 1987.
 73. Souquet, J.‐C., J. R., Grider, K. N. Bitar, and G. M. Makhlouf. Receptors for mammalian tachykinins on isolated intestinal smooth muscle cells. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G533–G538, 1985.
 74. Spindel, E. Mammalian bombesin‐like peptides. Trends Neurosci. 9: 130–133, 1986.
 75. Steigerwalt, R. W., I. D., Goldfine, and J. A. Williams. Characterization of cholecystokinin receptors on bovine gallbladder membranes. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G709–G714, 1984.
 76. Von Schrenck, P., T. Heinz‐Erian, T. Moran, D. H. Coy, J. D. Gardner, and R. T. Jensen. Characterization of receptor subtypes from bombesin (BN) and related peptides (Abstract). Gastroenterology 94: A482, 1988.
 77. Waterfield, A. A., R. W. J., Smokcum, J. Hughes, H. W. Kosterlitz, and G. Henderson. In vitro pharmacology of the opioid peptides, enkephalins and endorphins. Eur. J. Pharmacol. 43: 107–116, 1977.
 78. Yau, W. M., G. M., Makhlouf, L. E. Edwards, and J. T. Farrar. The action of cholecystokinin and related peptides on guinea pig small intestine. Can. J. Physiol. Pharmacol. 52: 298–303, 1974.

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How to Cite

Gabriel M. Makhlouf, John R. Grider. Receptors for Gut Peptides on Smooth Muscle Cells of the Gut. Compr Physiol 2011, Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology: 281-289. First published in print 1989. doi: 10.1002/cphy.cp060213