Neurotransmitters involved in the fast inhibitory junction potentials in mouse distal colon.
We investigated, in murine colon circular muscle, the role of adenosine 5'-triphosphate (ATP) and pituitary adenylate cyclase activating peptide (PACAP) as inhibitory neurotransmitters of the fast component of nerve-evoked inhibitory junction potential (fast IJP). Fast IJP was antagonised by apamin or suramin, abolished by desensitisation with the P2Y receptor agonist, adenosine 5'-O-2-thiodiphosphate (ADPbetaS), unaffected by desensitisation with P2X receptor agonist, alpha,beta-methylene ATP (alpha,beta-meATP), and reduced by PACAP-(6-38), a PACAP receptor antagonist. ATP induced membrane hyperpolarization resistant to tetrodotoxin, N(omega)-nitro-L-arginine methyl ester (L-NAME) or PACAP-(6-38), but antagonised by apamin, suramin, P2X and P2Y receptor desensitisation. PACAP-(1-27) caused membrane hyperpolarization antagonised by PACAP-(6-38), apamin and P2Y receptor desensitisation, reduced by tetrodotoxin, but not affected by L-NAME and by P2X receptor desensitisation. Therefore, in murine colon circular muscle, an ATP-like endogenous P2Y purinoceptor ligand is the final nonadrenergic, noncholinergic (NANC) inhibitory mediator involved in the generation of fast IJP. A neuromodulator role of PACAP in the inhibitory pathway is supposed.
Serio
Rosa
R
Dipartimento di Biologia cellulare e dello Sviluppo, Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy. rserio@unipa.it
Alessandro
Massimiliano
M
Zizzo
Maria Grazia
MG
Tamburello
Maria Pia
MP
Mulè
Flavia
F
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013873:Thionucleotides; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D001030:Apamin; C030812:adenosine 5'-O-(2-thiodiphosphate); D013779:Tetrodotoxin; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D019331:NG-Nitroarginine Methyl Ester