Summary
Physiological studies have shown that serotonin and 5-HT1A agonists can influence muscarinic function in the rabbit iris-ciliary body (ICB). The purpose of this study was to examine whether a direct interaction exists between muscarinic and 5-HT1A receptors in the ICB. At high concentrations, the 5-HT1A agonist 8-OH-DPAT attenuated the carbachol-induced stimulation of inositol phosphates (InsPs) production, but this was not blocked by the presence of 5-HT1A antagonists. In contrast, serotonin failed to influence carbachol-induced InsPs formation. Moreover, 8-OH-DPAT but not serotonin displayed affinity for [3H]QNB binding sites in the ICB. The combined data suggest that activation of 5-HT1A receptors in the ICB does not cause a modulation of muscarinic receptor-stimulated phosphoinositide turnover. The data instead suggest that, at high concentrations, 8-OH-DPAT acts as an antagonist at muscarinic receptors and in this way influences muscarinic receptor function. The mechanism of 5-HT-induced modulation of muscarinic function in the ICB therefore remains to be elucidated.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdel Latif AA (1989) Calcium-mobilizing receptors, polyphosphoinositides, generation of second messengers and contraction in the mammalian iris smooth muscle: historical perspectives and current status. Life Sci 45: 757–786
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14: 48–58
Barnett NL, Osborne NN (1993) The effect of serotonin on the rabbit isolated iris sphincter muscle. Curr Eye Res 12: 665–673
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Chidlow G, De Santis LM, Sharif NA, Osborne NN (1995) Characteristics of [3H]5-hydroxytryptamine binding to iris-ciliary body tissue of the rabbit. Invest Ophthalmol Vis Sci 36: 2238–2245
Claustre Y, Benavides J, Scatton B (1988) 5-HT1A receptor agonists inhibit carbachol-induced stimulation of phosphoinositide turnover in the rat hippocampus. Eur J Pharmacol 149: 149–153
Claustre Y, Benavides J, Scatton B (1991) Potential mechanisms involved in the negative coupling between serotonin 5-HT1A receptors and carbachol-stimulated phosphoinositide turnover in the rat hippocampus. J Neurochem 56: 1276–1285
Cole BJ, Jones GH, Turner JD (1994) 5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task. Psychopharmacology Berl 116: 135–142
Consolo S, Ladinsky H, Forloni GL, Tirelli AS, Garattini S (1980) Comparison of the effects of the stereoisomers of fenfluramine on the acetylcholine content of rat striatum, hippocampus and nucleus accumbens. J Pharm Pharmacol 32: 201–203
Crist J, Surprenant A (1987) Evidence that 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT) is a selective alpha 2-adrenoceptor antagonist on guinea-pig submucous neurones. Br J Pharmacol 92: 341–347
De Vivo M, Maayani S (1986) Characterization of the 5-hydroxytryptamine 1a receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther 238: 248–253
Fowler CJ, Ahlgren PC, Brannstrom G (1991) Antagonism by 8-hydroxy-2 (di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells. Life Sci 48: 959–967
Fozard JR, Kilbinger H (1985) 8-OH-DPAT inhibits transmitter release from guineapig enteric cholinergic neurons by activating 5-HT1A receptors. Br J Pharmacol 67: 601P
Galligan JJ (1992) Differential inhibition of cholinergic and noncholinergic neurogenic contractions by 5-hydroxytryptamine1A receptor agonists in guinea pig ileum. J Pharmacol Exp Ther 260: 306–312
Gherezghiher T, March WF, Nordquist RE, Koss MC (1986) Laser-induced glaucoma in rabbits. Exp Eye Res 43: 885–894
Hill SJ, Kendall DA (1989) Cross-talk between different receptor-effector systems in the mammalian CNS. Cell Signal 1: 135–141
Hirose A, Sasa M, Akaike A, Takaori S (1990) Inhibition of hippocampal CA1 neurons by 5-hydroxytryptamine, derived from the dorsal raphe nucleus and the 5-hydroxytryptamine1A agonist SM-3997. Neuropharmacology 29: 93–101
Hong Y, Krnjevic K (1989) Serotonin blocks the facilitatory action of muscarinic and nicotinic agents in the hippocampus in vivo. Can J Physiol Pharmacol 67: 47–53
Kaufman PL (1984) Mechanisms of actions of the cholinergic drugs in the eye. In: Drance SM, Neufeld AH (eds) Glaucoma: applied pharmacology in medical treatment. Grune & Stratton, Orlando, pp 395–427
Mallorga P, Babilon RW, Buisson S, Sugrue MF (1989) Muscarinic receptors of the albino rabbit ciliary process. Exp Eye Res 48: 509–522
Miichi H, Nagataki S (1983) Effects of pilocarpine, salbutamol, and timolol on aqueous humor formation in cynomolgus monkeys. Invest Ophthalmol Vis Sci 24: 1269–1275
Moro F, Scapagnini U, Scaletta S, Drago F (1981) Serotonin nerve endings and regulation of pupillary diameter. Ann Ophthalmol 13: 487–490
Munson PJ, Rodbard D (1980) Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 107: 220–239
Nardin GF, Zimmerman TJ, Zalta AH, Felts K (1989) Ocular cholinergic agents. In: Ritch R, Shields MB, Krupin T (eds) The glaucomas, vol 1. Mosby, St. Louis, pp 515–521
Osborne NN, Tobin AB (1987) Serotonin-accumulating cells in the iris-ciliary body and cornea of various species. Exp Eye Res 44: 731–745
Osborne NN, Chidlow G (1996) Do beta-adrenoceptors and serotonin 5-HT1A receptors have similar functions in the control of intraocular pressure (IOP) in the rabbit? Ophthalmologica 210: 308–314
Raymond JR, Albers FJ, Middleton JP (1992) Functional expression of human 5-HT1A receptors and differential coupling to second messengers in CHO cells. Naunyn Schmiedebergs Arch Pharmacol 346: 127–137
Riekkinen P Jr (1994) 5-HT1A and muscarinic acetylcholine receptors jointly regulate passive avoidance behavior. Eur J Pharmacol 262: 77–90
Samochocki M, Strosznajder J (1995) The negative coupling between serotonin and muscarinic receptor(s) for arachidonic acid and inositol phosphates release in brain cortex synaptoneurosomes. Effect of aging. Neurochem Int 26: 571–578
Schoeffter P, Hoyer D (1988) Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus. Br J Pharmacol 95: 975–985
Spencer DG Jr, Horvath E, Traber J (1986) Direct autoradiographic determination of M1 and M2 muscarinic acetylcholine receptor distribution in the rat brain: relation to cholinergic nuclei and projections. Brain Res 380: 59–68
Tobin AB, Unger W, Osborne NN (1988) Evidence for the presence of serotonergic nerves and receptors in the iris-ciliary body complex of the rabbit. J Neurosci 8: 3713–3721
Uusitalo H, Lehtosalo J, Laakso J, Harkonen M, Palkama A (1982) Immunohistochemical and biochemical evidence for 5-hydroxytryptamine containing nerves in the anterior part of the eye. Exp Eye Res 35: 671–675
Verge D, Daval G, Marcinkiewicz M, Patey A, Mestikawy S, Gozlan H, Hamon M (1986) Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats. J Neurosci 6: 3474–3482
Woldemussie E, Feldmann BJ, Chen J (1993) Characterization of muscarinic receptors in cultured human iris sphincter and ciliary smooth muscle cells. Exp Eye Res 56: 385–392
Zifa E, Fillion G (1992) 5-Hydroxytryptamine receptors. Pharmacol Rev 44: 401–458
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chidlow, G., Osborne, N.N. Antagonism of muscarinic receptors in the rabbit iris-ciliary body by 8-OH-DPAT and other 5-HT1A receptor agonists. J. Neural Transmission 104, 1015–1025 (1997). https://doi.org/10.1007/BF01273315
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01273315