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Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

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Most of the nerve fibers enter the pancreas along the arteries (Miller, 1981; Woods<br />

& Porte, 1974). Unmyelinated nerve fibers are found in the neighborhood of all<br />

islet cell types at the periphery <strong>and</strong> within the islet. At some distance from the<br />

islets, glial Schwann cells often form a thin sheet around nerve fibers on their<br />

travel toward <strong>and</strong> within the islet. In the vicinity of islet cells, however, it is not<br />

rare to see some nerve fibers lacking this glial protection <strong>and</strong> coming close to or<br />

ending blindly 20–30 nm from the endocrine cells (Bock, 1986; Fujita &<br />

Kobayashi, 1979; Legg, 1967; Radke & Stach, 1986; Shorr & Bloom, 1970;<br />

Watari, 1968).<br />

The preganglionic fibers of the parasympathetic limb originate from<br />

perikarya located in the dorsal motor nucleus of the vagus (Berthoud et al., 1990;<br />

Berthoud & Powley, 1991; Chen et al., 1996) <strong>and</strong> possibly also in the nucleus<br />

ambiguus (Luiten et al., 1986) which are both under the control of the<br />

hypothalamus. They are organized in well separated branches traveling within the<br />

vagus nerves (cranial nerve X) <strong>and</strong> through the hepatic, gastric (Berthoud et al.,<br />

1990; Berthoud & Powley, 1991) <strong>and</strong> possibly celiac branches of the vagus<br />

(Kinami et al., 1997). They reach intrapancreatic ganglia that are dispersed in the<br />

exocrine tissue. These ganglia send unmyelinated postganglionic fibers toward the<br />

islets. Preganglionic vagal fibers release acetylcholine that binds to nicotinic<br />

receptors on intraganglionic neurons. Postganglionic vagal fibers release several<br />

neurotransmitters: acetylcholine, Vasoactive Intestinal Peptide (VIP), gastrinreleasing<br />

peptide (GRP), nitric oxide (NO) <strong>and</strong> pituitary adenylate cyclaseactivating<br />

polypeptide (PACAP) (Havel et al., 1997, Ahren et al., 1999; Love &<br />

Szebeni, 1999; Wang et al., 1999; Ahren, 2000; Myojin et al., 2000). Cholinergic<br />

terminals are found in the neighborhood of all islet cell types at the periphery <strong>and</strong><br />

within the islet (Van der Zee et al., 1992). The importance of the cholinergic<br />

innervation of the endocrine pancreas is attested by the presence of a 10-fold<br />

higher activity of choline acetyltransferase <strong>and</strong> acetylcholine esterase (the<br />

enzymes involved in the synthesis <strong>and</strong> the degradation of acetylcholine<br />

15

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