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Modulation of neurotransmitter release by opioid receptors in enteric neurons
Pharmacological
317
Research, Vol. 26, Supplement I, 1992
BETA-CASOYORPHINS ANDNDRPHlNE INHIBIT PliDSPBOLIPASE A2 ACTIVITYANDINCREASE DIACYLGLYCEROL PRDWTIDN IN RATSTONACB CORPUS NUCOSA Parall E.,Aatanilli L. Institute al Nodical PharuacalagyJoiversity of Role-La Sapiesza
ir PGEZpeg B-casouorhin l-518 ag/e IPI
B-casomorp %in l-4 arldel8 u /kg IP) Yarphine llcl (20 @kg IP) Saline
PL irk 9.83” (0.091 Kr 9:27**
(2.68)
‘%’ (0:23 I
Oleate nil 7 .?8” LO.221 5.71”
(0.211 6.55”
‘E CO:181
DC1 0.129 (0.014l
0.45** (0.016) 0.25”’ (0.021 ~11%
At variance sith the behavior of PGE2,tbe breakdownof phosphatidylcholine uas evenly inhibited by B-casouarphins and rarphiuo. DGproduction wassharp!y increased by all the oplaids. DS role in gastric protection is 80s under investigation. LlIParolf E.World Rev.Nutr.Dlet:55,5? 1988. t2lParali E.,Antoniili L. Pharaacol. Research. 1991 (in press1
MODULATION OF NEUROTRANSMIITER RELEASE BY OPIOID RECEPTORS IN ENTERIC NEURONS F. Marina, F. Greta,F. De Ponti, S. Lecchini & G.M. Frigo Department of Internal Medicine and Therapeutics,University of Pavia, Pavia, Italy. There is now compelling evidencethat opioids function as neurotransmittersand/or neuromodulatorsin the gastrointestinal tract. Most of the studies carried out so far have dealt with the role of opioids in modulating small bowel motility, while the colon, an organ under tonic neurogenic inhibition, has received relatively little attention. The aim of the present study was to assessthe effect of rmloxone on acetylchohne (ACh) and noradrenaline (NA) release in the guinea-pig distal colon. Furthemore, we studied the effects of naloxone on electrically induced contractionsof the longitudinal muscle and nonadrenergic non-choline@ (NANC) relaxations of the circular muscle. Endogenous ACh release was measured in basal conditions and after electrical stimulation (1 Hz, 1 ms, 450 mA). NA release was measuredfrom colonic segmentsdeprivedof the mucosaand stimulated electricalIy (4 Hz, lms, 350-700 mA). Naloxone dose-dependentlyincreasedbasal and electrically evoked ACh releasewith EC50 values of 347 (204-588) and 78 (18-347) nM, respectively. Naloxone also dose-dependently enhanced electrically evoked NA releasewith an EC50 value of 6 (0.25-149) r&i. Naloxone (1 pM) did not tiect electrically induced contractions of the longitudinal muscle, while it enhancedNANC relaxations in a frequency-dependentmanner. The increasesin NANC relaxation induced by 1, 2 and 4 Bz stimulation were 7 f 1 %, 32 f 7 % and 50 * 4 %, respectively.The present study, showing a facilitatory effect of naloxone on ACh and NA release, substantiates the hypothesis that opioids tonically inhibit neurotransmitter releasein the guinea-pig distal colon. This tonic restraint seemsto operate not only on excitatory cholinergic pathwaysbut also on adrenergicand NANC inhibitory pathways.
317
Research, Vol. 26, Supplement I, 1992
BETA-CASOYORPHINS ANDNDRPHlNE INHIBIT PliDSPBOLIPASE A2 ACTIVITYANDINCREASE DIACYLGLYCEROL PRDWTIDN IN RATSTONACB CORPUS NUCOSA Parall E.,Aatanilli L. Institute al Nodical PharuacalagyJoiversity of Role-La Sapiesza
ir PGEZpeg B-casouorhin l-518 ag/e IPI
B-casomorp %in l-4 arldel8 u /kg IP) Yarphine llcl (20 @kg IP) Saline
PL irk 9.83” (0.091 Kr 9:27**
(2.68)
‘%’ (0:23 I
Oleate nil 7 .?8” LO.221 5.71”
(0.211 6.55”
‘E CO:181
DC1 0.129 (0.014l
0.45** (0.016) 0.25”’ (0.021 ~11%
At variance sith the behavior of PGE2,tbe breakdownof phosphatidylcholine uas evenly inhibited by B-casouarphins and rarphiuo. DGproduction wassharp!y increased by all the oplaids. DS role in gastric protection is 80s under investigation. LlIParolf E.World Rev.Nutr.Dlet:55,5? 1988. t2lParali E.,Antoniili L. Pharaacol. Research. 1991 (in press1
MODULATION OF NEUROTRANSMIITER RELEASE BY OPIOID RECEPTORS IN ENTERIC NEURONS F. Marina, F. Greta,F. De Ponti, S. Lecchini & G.M. Frigo Department of Internal Medicine and Therapeutics,University of Pavia, Pavia, Italy. There is now compelling evidencethat opioids function as neurotransmittersand/or neuromodulatorsin the gastrointestinal tract. Most of the studies carried out so far have dealt with the role of opioids in modulating small bowel motility, while the colon, an organ under tonic neurogenic inhibition, has received relatively little attention. The aim of the present study was to assessthe effect of rmloxone on acetylchohne (ACh) and noradrenaline (NA) release in the guinea-pig distal colon. Furthemore, we studied the effects of naloxone on electrically induced contractionsof the longitudinal muscle and nonadrenergic non-choline@ (NANC) relaxations of the circular muscle. Endogenous ACh release was measured in basal conditions and after electrical stimulation (1 Hz, 1 ms, 450 mA). NA release was measuredfrom colonic segmentsdeprivedof the mucosaand stimulated electricalIy (4 Hz, lms, 350-700 mA). Naloxone dose-dependentlyincreasedbasal and electrically evoked ACh releasewith EC50 values of 347 (204-588) and 78 (18-347) nM, respectively. Naloxone also dose-dependently enhanced electrically evoked NA releasewith an EC50 value of 6 (0.25-149) r&i. Naloxone (1 pM) did not tiect electrically induced contractions of the longitudinal muscle, while it enhancedNANC relaxations in a frequency-dependentmanner. The increasesin NANC relaxation induced by 1, 2 and 4 Bz stimulation were 7 f 1 %, 32 f 7 % and 50 * 4 %, respectively.The present study, showing a facilitatory effect of naloxone on ACh and NA release, substantiates the hypothesis that opioids tonically inhibit neurotransmitter releasein the guinea-pig distal colon. This tonic restraint seemsto operate not only on excitatory cholinergic pathwaysbut also on adrenergicand NANC inhibitory pathways.