Effects of calcitonin gene-related peptide on opossum esophageal smooth muscle

Pharmacologic Characterization of Intrinsic Mechanisms Controlling Tone and Relaxation of Porcine Lower Esophageal Sphincter

“…Nitric oxide, ATP, and PACAP induced a complete LES relaxation, and CORM-1 and VIP were clearly less efficient, as observed in porcine gastric fundus (Colpaert et al, 2002). In contrast, the same dose of CGRP that relaxed LES strips in opossums failed to relax our preparation despite the similarity between both species in the EFS-induced responses (Uc et al, 1997). These discrepancies could be explained by species differences and/or CGRP acting through more complex neural circuits in "in vivo" studies (Rattan et al, 1988).…”

“…We only included clasp strips that developed active tension and relaxed during stimulation of inhibitory motor neurons, ensuring that we had selected LES strips with intact innervation. We tested the effect of a nitric oxide donor, VIP, ATP, PACAP, a carbon monoxide donor, and CGRP because these substances colocalize in esophageal inhibitory motor neurons (Ny et al, 1995a;Uc et al, 1997). Colocalized substances can participate as neuromodulators, neurotransmitters, or with neurotrophic effects (Burnstock, 2004).…”

“…Concentration-response curves for CORM-1 were obtained in a cumulative fashion. Concentrations of neurotransmitters were selected according to previous studies, most on LES (Yamato et al, 1992;Ny et al, 1995b;Uc et al, 1997Uc et al, , 1999Rattan et al, 2004). We used 1 nM to 3 M for sodium nitroprusside, 1 nM to 1 M for VIP, PACAP, and CGRP; 10 M to 30 mM for ATP; and 1 M to 1 mM for CORM-1.…”

“…Vasoactive intestinal peptide (VIP), nitric oxide, ATP, pituitary adenylate cyclase-activating peptide (PACAP), carbon monoxide, and calcitonin gene-related peptide (CGRP) have been proposed as putative neurotransmitters for these inhibitory enteric motor neurons in LES on the basis of morphological and physiological studies. Colocalization of these neurotransmitters and/or their synthesizing enzymes on inhibitory enteric motor neurons of the upper gastrointestinal tract including LES has been described by immunohistological and other morphological studies (Ny et al, 1994(Ny et al, , 1995aUc et al, 1997;Werkstrom et al, 1997). Physiological and pharmacological studies have demonstrated the direct effects or characterized the actions of these neurotransmitters after stimulation of inhibitory LES motor neurons (Ny et al, 1995bUc et al, 1997;Yuan et al, 1998;Imaeda and Cunnane, 2003).…”

“…Colocalization of these neurotransmitters and/or their synthesizing enzymes on inhibitory enteric motor neurons of the upper gastrointestinal tract including LES has been described by immunohistological and other morphological studies (Ny et al, 1994(Ny et al, , 1995aUc et al, 1997;Werkstrom et al, 1997). Physiological and pharmacological studies have demonstrated the direct effects or characterized the actions of these neurotransmitters after stimulation of inhibitory LES motor neurons (Ny et al, 1995bUc et al, 1997;Yuan et al, 1998;Imaeda and Cunnane, 2003). However, evidence suggests that nitric oxide from neural sources is the major contributor to LES relaxation (Murray et al, 1991;Tottrup et al, 1991;Gonzalez et al, 2004), and the relative physiological contribution of other neurotransmitters remains unclear.…”