Restoration by VIP of the carbachol-stimulated Cl- secretion in TTX-treated guinea pig distal colon.
To determine if vasoactive intestinal peptide (VIP) restores neural activity from tetrodotoxin (TTX) blockade, we studied the effects of VIP and related agents on carbachol (Cch)-induced Cl(-) secretion in control-isolated guinea pig distal colon and in that treated with TTX. The short circuit current (I(sc)) increased dose-dependently after serosal applications of Cch (10(-6) - 2 x 10(-5) M) and VIP (5 x 10(-9) - 10(-7) M). But no additive or synergistic increase in I(sc) was observed. Cch- and VIP-induced I(sc) was completely abolished by a serosal application of TTX (10(-6) M). However, a serosal application, not mucosal, of VIP (10(-7) M) and 8-bromo-cAMP (10(-3) M) restored the Cch-stimulated, TTX-inhibited I(sc) by 113% and 75.8%, respectively. Furthermore, mucosal and serosal applications of forskolin (aden late cyclase activator) restored the I(sc) by 43.9% and 65.3%, respectively. The restored I(sc) was completely abolished by atropine (muscarinic receptor antagonist). These results suggest that VIP may restore the cholinergic activity by increasing the level of intracellular cAMP, and that cholinergic neuron is very likely to be responsible for the regulation of Cl(-) secretion at neuroepithelial junctions. The exact mechanism of VIP's effect on the TTX-inhibited epithelial Cl(-) secretion, and its possible usefulness in the treatment of TTX-induced pathophysiological conditions, remain to be determined.
Kokubo
A
A
Department of Physiology, Kitasato University School of Medicine, Sagamihara, Japan.
Yasuoka
Y
Y
Nishikitani
M
M
Saigenji
K
K
Kawahara
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D044683:Colon, Descending / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011042:Poisons / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002712:Chlorides; D018678:Cholinergic Agents; D005765:Gastrointestinal Agents; D018377:Neurotransmitter Agents; D011042:Poisons; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001285:Atropine; D002217:Carbachol