Localisation and neural control of the release of calcitonin gene-related peptide (CGRP) from the isolated perfused porcine ileum

By immunohistochemistry, CGRP-like immunoreactive (CGRP-LI) nerve fibres we re found in the lamina propria along small vessels and in the lamina muscul aris mucosae in the porcine ileum. Immunoreactive nerve cell bodies were fo und in the submucous and myenteric plexus. Upon HPLC-analysis of ileal extr acts, CGRP-LI corresponded entirely to porcine CGRP plus smaller amounts of oxidised CGRP. Using isolated vascularly perfused segments of the ileum, w e studied the release of CGRP-LI in response to electrical stimulation of t he mixed extrinsic periarterial nerves and to infusion of different neurobl ockers. In addition, the effect of infusion of capsaicin was studied. The b asal output of CGRP-LI was 2.9 +/- 0.7 pmol/5 min (mean +/- S.D.). Electric al nerve stimulation (8 Hz) significantly increased the release of CGRP-LI to 167 +/- 16% (mean +/- S.E.M.) of the basal output (n = 13). This respons e was unaffected by the addition of atropine (10(-6) M). Nerve stimulation during infusion of phentolamine (10(-5) M) with and without additional infu sion of atropine resulted in a significant further increase in the release of CGRP-LI to 261 +/- 134% (n = 5) and 240 +/- 80% (n = 9), respectively. T his response was abolished by infusion of hexamethonium (3 X 10(-5) M). Inf usion of capsaicin (10-5 M) caused a significant increase in the release of CGRP-LI to 485 +/- 82% of basal output (n = 5). Our results suggest a dual origin of CGRP innervation of the porcine ileum (intrinsic and extrinsic). The intrinsic CGRP neurons receive excitatory input by parasympathetic, po ssibly vagal, preganglionic fibres, via release of acetylcholine acting on nicotinic receptors. The stimulatory effect of capsaicin suggests that CGRP is also released from extrinsic sensory neurons. (C) 2001 Elsevier Science B.V. All rights reserved.