Sympathetic denervation-induced changes in G protein expression in enteric neurons of the guinea pig colon.
Chronic sympathetic denervation entails subsensitivity to alpha(2)-adrenoceptor agonists and supersensitivity to kappa- and mu-opioid receptor agonists modulating cholinergic neurons in the guinea pig colon. A possible role for signal transduction G proteins in contributing to development of these sensitivity changes was investigated. Pertussis toxin (PTX), a blocker of the G(i/o)-type family of G proteins significantly reduced the inhibitory effects of UK14,304 (alpha(2)-adrenoceptor agonist), U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on acetylcholine (ACh) overflow in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals. In this experimental condition, immunoblot analysis revealed reduced levels of G(alphao), G(alphai2), G(alphai3) and G(beta) in myenteric plexus synaptosomes. On reverse, synaptosomal levels of G(alphai1) and G(alphaz), a PTX-insensitive G-protein, increased after chronic ablation of the sympathetic pathways. These data suggest that changes in the function and expression of inhibitory G proteins coupled to alpha(2)-adrenoceptors, kappa- and mu-opioid receptors occur in the myenteric plexus of the guinea pig colon after chronic sympathetic denervation. The possibility that regulation of G proteins represents one of the biochemical mechanisms at the basis of the changes in sensitivity of enteric cholinergic neurons to alpha(2)-adrenoceptor, kappa- and mu-opioid receptor agonists is discussed.
Giaroni
Cristina
C
Clinical and Applied Pharmacology Centre, Universities of Insubria and Pavia, via O. Rossi 9, I-21100 Varese, Italy.
Zanetti
Elena
E
Vanti
Alessandro
A
Canciani
Luca
L
Lecchini
Sergio
S
Frigo
Gianmario
G
D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017763:Autonomic Denervation; D044482:Benzeneacetamides; D000068438:Brimonidine Tartrate; D002458:Cell Fractionation; D003106:Colon / Q000294:innervation*; D004336:Drug Antagonism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D044482:Benzeneacetamides; D011759:Pyrrolidines; D011810:Quinoxalines; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000068438:Brimonidine Tartrate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C045444:U 69593; D000109:Acetylcholine