The role of cholecystokinin in ganglionic transmission in the guinea‐pig gall‐bladder.

Abstract

SUMMARY1. The effects of cholecystokinin (CCK) on intact guinea-pig gall-bladder ganglia were investigated with intracellular, single-electrode current-and voltage-clamp recording techniques.2. Cholecystokinin octapeptide (CCK-8; 0 01-100 nM) increased the amplitude of the fast excitatory postsynaptic potential (EPSP) that was evoked by stimulation of interganglionic fibre tracts. In most cases, neurones that exhibited subthreshold EPSPs in normal Krebs solution fired action potentials in the presence of CCK-8. In a low Ca2+/high Mg2" solution, CCK-8 caused a 3-fold increase in the amplitude of fast EPSPs.3. The amplitude of the evoked excitatory postsynaptic current (EPSC) was increased by CCK-8 (0 01-100 nM) in a concentration-dependent manner. The effect was maximal at 10 nM.4. Cholecystokinin octapeptide caused a 3-fold increase in the quantal content of the EPSP in a low Ca2+/high Mg2+ solution, but had no effect on the quantal size.5. The specific CCK-A receptor antagonist, MK-329 (formerly L-364,718; l0 nM), reversibly blocked the facilitatory effect of CCK-8 on ganglionic transmission. However, the specific CCK-B receptor antagonist, L-365,260 (10 nM), did not alter the presynaptic facilitatory effect of CCK-8. 6. The response of gall-bladder neurones to exogenously applied ACh was hot modified by CCK-8.7. Application of CCK-8, by superfusion (0 001-100 nM) or by pressure microejection (100 /am), had no effect on the membrane potential, membrane conductance, action potential, or threshold of gall-bladder neurones.8. Immunohistochemistry was employed to determine whether the actions of CCK could be elicited by release of the peptide from nerve terminals within the ganglionated plexus of the gall-bladder. Immunoreactivity for CCK was not detected in the ganglionated plexuses of the gall-bladder, but CCK immunoreactivity was plentiful in control preparations of intestinal myenteric and submucosal plexuses.9. These results show that CCK has a presynaptic facilitatory effect on fast synaptic transmission in guinea-pig gall-bladder ganglia, and that this effect is mediated by presynaptic CCK-A receptors. Furthermore, it appears that such an MS 8804 effect would normally occur in response to hormonal CCK, rather than CCK that is released from nerve terminals.

Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice

“…However, Mawe (1991) reported previously that neural elements expressing CCK1 receptors might be involved in the response of the gallbladder to hormonal CCK in guinea pigs. The present study confirmed the abundant localization of CCK1 receptors along the plasma membrane of smooth muscle fibers in the mouse gallbladder.…”

“…Besides the direct stimulation by CCK, indirect pathways via the vagal nerve have been proposed for the regulation of the pancreas and gallbladder (Mawe 1991;Owyang and Logsdon 2004;Singer and Niebergall-Roth 2009). CCK also plays a role in the intestinal phase in the control of gastric functions that negatively regulate meal-stimulated gastric acid secretion and gastrin release (Lloyd et al 1992a, b), possibly via somatostatin release (Schmidt et al 1994).…”

Noradrenaline as a presynaptic inhibitory neurotransmitter in ganglia of the guinea‐pig gall‐bladder.

“…and since the terminals of vagal efferent fibres in gall-bladder ganglia may be a crucial site of the action of CCK (Hanvu. Dodds, Layman & Takahashi, 1990; Bauer et al 1991;Mawe, 1991), it is not surprising to find that the vagal terminals might also be a target of the sympathetic inhibitory input to the gall-bladder.…”

“…The major hormone affecting tissue of the gall-bladder is cholecystokinin (CCK). Cholecystokinin is secreted by glands in the submucosal layer of the duodenum, and is likely to act both directly on gall-bladder tissues as well as in gall-bladder ganglia (see Mawe, 1991). The vagus nerve provides the major neural input to the gall-bladder.…”

Tachykinins as mediators of slow EPSPs in guinea‐pig gall‐bladder ganglia: involvement of neurokinin‐3 receptors.

“…It is now commonly accepted that ganglionic transmission can be modulated by pre-and postsynaptic actions of neurotransmitters, circulating hormones and immune-mediated agents. For example, in the gall-bladder, hormonal CCK and neurally released noradrenaline can act presynaptically to facilitate or inhibit nicotinic synaptic transmission, respectively (Mawe, 1991;. Also, capsaicin-sensitive afferent fibres have been shown to have a role as axonal reflex modulators of ganglionic transmission in several systems, including sympathetic para-and prevertebral ganglia, enteric ganglia and respiratory ganglia (Otsuka & Yoshioka, 1993).…”