Muscarinic inhibition of [₃H]‐noradrenaline release on rabbit iris in vitro: effects of stimulation conditions on intrinsic activity of methacholine and pilocarpine

Abstract

1 Rabbit isolated irides were loaded with [3H]-noradrenaline and superfused with Tyrode solution. The inhibition by the muscarinic agonists (±)-methacholine and pilocarpine of the [3H]-noradrenaline overflow into the superfusate evoked by field stimulation (pulses of 1 ms duration, 75 mA) was measured as an index of activation of presynaptic muscarinic receptors. 2 The fractional rate of release per pulse during the first stimulation period (SI) was low with 360 pulses at 3 Hz, intermediate with 360 pulses at 10Hz and high with 1200 pulses at 10Hz. Upon repetitive stimulation (7 periods at 20 min intervals), the fractional rates of release per pulse during S7 no longer differed, suggesting a 'long-term' regulation of [3H]-noradrenaline release depending on the stimulation conditions. 5 Depending on the concentration, pilocarpine reduced the [3H]-noradrenaline overflow evoked by 360 pulses at 3Hz up to 63%. However, at 10Hz stimulation frequency the compound was inactive as an agonist but competitively antagonized the presynaptic inhibition induced by methacholine. The KB under the latter condition (0.95 Mm) was very close to the EC50 value determined at 3 Hz (0.85 pM). 6 The results demonstrate a muscarinic inhibition of noradrenaline release from the rabbit isolated iris. The activation by pilocarpine of the presynaptic receptors provides an alternative explanation for the miosis induced in the rabbit in vivo, which might be the result of a decreased sympathetic tone in the iris dilator muscle.

Presynaptic muscarinic receptors inhibiting endogenous noradrenaline release in the portal vein of the freely moving rat

“…This could, however, indicate functional inhibition of NA overflow at the sympathetic varicosity by endogenous acetylcholine released during co-stimulation of parasympathetic neurones present in the portal vein nervous plexus (Boekelaar, 1985). A similar moderate atropine (0.1 pM)induced enhancement of [3H]-NA overflow was found by Bognar et al (1988) during electrical field stimulation (10 Hz, 1 ms and 75 mA) of the rabbit iris in vitro.…”

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea‐pig colon

“…These ®ndings indicate that, in our experimental conditions, endogenous acetylcholine enhances NA release through the activation of muscarinic receptors and indirect evidence suggests that the M 1 subtype is the main receptor involved. Muscarinic modulation of NA release has been demonstrated in a wide range of tissues, including heart and blood vessels (Muscholl, 1980;Vanhoutte & Levy, 1980), trachea (Racke , BaÈ hting, Brunn, Elsner & Wessler, 1991, iris (Bognar, Pallas, Fuder & Muscholl, 1988), vas deferens (Grimm et al, 1994), stomach (Yokotani & Osumi, 1993) and ileum (Alberts & StjaÈ rne, 1982). In particular, muscarinic facilitation of NA release through M 1 receptors has been reported in guinea-pig carotid arteries (Casado, Marin & Salaices, 1992;Casado, Sevilla, Alonso, MarõÁ n & Salaices, 1994) and in mouse (Costa & Majewski, 1991;Costa, Barrington & Jajewski, 1993) and rabbit atria (Habermeier-Muth, Altes, Forsyth & Muscholl, 1990).…”

Autonomic Control of the Eye

“…Importantly, release of 3H-noradrenaline is inhibited when the muscarinic receptors (M2 subtype) on sympathetic nerve endings in the human iris-ciliary body (175) or whole iris of other mammals (44, 98) are activated by muscarinic agonists (251). Thus, conceivably parasympathetic innervation of the sphincter pupillae can potentially partially antagonize the effect of sympathetic innervation of this tissue.…”