Modulation of neurotransmitter release by opioid μ- and κ-receptors from adrenergic terminals in the myenteric plexus of the guinea-pig colon: effect of α2-autoreceptor blockade (original) (raw)
Related papers
Neuroscience Letters, 1995
We have studied the effects of p-and /cc-opioid receptor blockade on endogenous acetylcholine and noradrenaline overflow from the myenteric plexus of the guinea-pig isolated colon. Cyprodime (putative p-selective antagonist) and nor-binaltorphimine (K-selective antagonist) had a concentration-dependent facilitatory effect on both acetylcholine and noradrenaline overflow. Moreover, in colonic specimens obtained from sympathetically denervated animals, the effect of opioid antagonists on acetylcholine overflow was significantly higher with respect to normal preparations. Evidence is thus given in favour of an involvement of p-and /c-opioid receptor pathways in the tonic modulation of neurotransmitter release at the colonic level. Enhanced sensitivity to the effect of p and K antagonists after chronic sympathetic denervation is strongly suggestive for the existence of a functional link between opioid and adrenergic pathways in this model.
British Journal of Pharmacology, 1990
Brief exposure for 2 min of guinea-pig isolated ileum to [Met5]enkephalin (MEnk) and noradrenaline has been shown previously to produce withdrawal contractures on washout of the agonist or addition of naloxone (MEnk) or phentolamine (noradrenaline). 2 The present study was undertaken to investigate firstly, whether other putative neurotransmitters and/or related drugs which inhibit transmitter release also produced withdrawal responses following 2 min contact with the ileum and secondly, whether they affected the opioid withdrawal response. 3 Adenosine (1-5 uM), but not U-50,488H (1-5 pM), somatostatin (0.01-5 pM), ocreotide (1-5 UM), baclofen (1-25uMm) or dopamine (5, 5O#M), produced a contracture on washout following 2min contact with the ileum. The adenosine (5,UM) washout contracture, in common with MEnk and noradrenaline washout contractures, was inhibited by the substance P antagonist, spantide (10pM). 4 Added 30s before washout at a concentration of 5pgM, noradrenaline, U-50,488H, adenosine, somatostatin and ocreotide significantly inhibited the washout withdrawal response following 2 min contact of the ileum with MEnk, 1 M. A higher concentration of baclofen, 250,UM, also inhibited this response. 5 The naloxone (1 pM)-precipitated withdrawal response following contact of the ileum with MEnk, 1 ,UM, for 2 min, was inhibited only by noradrenaline (5pM) and U-50,488H (5pM). 6 It is concluded that during naloxone-precipitated opioid withdrawal an additional population of enteric motor neurones is recruited which is not involved in the washout withdrawal response and these neurones have less diversity of presynaptic receptors mediating inhibition of transmitter release than cholinergic motor neurones.
Journal of Autonomic Pharmacology, 1997
1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA over¯ow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 mM) signi®cantly enhanced spontaneous endogenous NA over¯ow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M 1 -selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M 2 -selective antagonist) inhibited NA over¯ow in a concentration dependent manner, with the following EC 50 values: 131.74 (18.19±953.96), 101.62 (58.83±175.60), 150 (60±330), 30 (5±170) nM, respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M 1 -and M 3 -selective antagonist) had no signi®cant eect up to 100 mM. 3 The muscarinic agonist oxotremorine inhibited NA over¯ow in a concentration dependent manner, with an EC 50 value of 0.67 (0.30±1.51) mM. The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine 4 4-DAMP 44 AF-DX 116. 4 In the presence of 3 mM tetrodotoxin (TTX), the eect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, signi®cantly enhanced NA over¯ow. 5
Physiological analysis of δ opioid receptors in the guinea pig myenteric plexus
Life Sciences, 1982
Ilea taken from guinea pigs that had been chronically exposed to morphine exhibit a greater tolerance to morphine and normorphine than to the opioid peptides D-ala2-D-leu5-enkephalin (DADLE) or D-met2-pro5enkephalinamide (DMPE). This differential tolerance strongly implies the existence of at least two different types of opioid receptor in the guinea pig myenteric plexus or two different mechanisms of interaction between opioids and their receptor complex.
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994
In order to clarify whether adrenoceptors in the guinea-pig distal colon are under sympathetic control, we assessed possible variations in the sensitivity to adrenoceptor agonists after blockade of neuronal catecholamine uptake mechanisms by desipramine (DMI). First, experiments were carried out to investigate the effects of DMI added in the organ bath on propulsion velocity, endogenous and [3H] prelabelled acetylcholine overflow, electrically evoked noradrenaline overflow and longitudinal smooth muscle tone. Secondly, we studied the effects of adrenoceptor agonists on the above parameters in untreated animals and in animals chronically treated with DMI.
Journal of Autonomic Pharmacology, 1993
The short-circuit current, which indicates net chloride secretion under the present experimental condition, was stimulated by PGE, plus theophylline in the guinea-pig colonic mucosa in vitro. 2 It was dose-dependently inhibited by up to 65% at 1 ymol 1-I by the K-selective opioid agonist, U69593. The y-selective opioid agonist, DAGO, was inactive, while the d-selective opioid agonist DPDPE displayed about 20% inhibition at 1 pmol 1-I. Basal secretion was not inhibited by the three agonists to any biologically relevant degree. 3 The p-selective opioid antagonist, CTOP-NH2 (0.1 ymol l-l), partially inhibited PGE, plus theophylline-stimulated net chloride secretion, suggesting that endogenous opioid peptides enhance secretion. The non-selective opioid antagonist, naloxone, at the high concentration of 100 ymoi 1-I also partially inhibited net chloride secretion and prevented, upon pre-administration, any further effect of CTOP-NH2. This confirms the opioid nature of the receptor affected by CTOP-NH2 in vitro. 4 The antisecretory effect of CTOP-NH2 has been confirmed in the rat in vivo using jejunal enteropooling upon continuous stimulation by PGE2. A high dose (1 mg kg-' s.c.) of naloxone tended to either inhibit the diarrhoeal action of a high dose of PGE, (79.1 ng min-' i.a.) or augment the diarrhoea1 action of a lower dose of PGE2 (3 1.6 ng min-l i.a.). The contrasting effects of naloxone may be due to endogenous activation of both p and K opioid receptors at high doses of PGE, but only p opioid receptors at low doses. In either case, no further inhibition by CTOP-NH2 was observed after pretreatment with naloxone, proving the opioid nature of the receptor affected by CTOP-NH2 in vivo.
Gastroenterology, 2002
Background&Aims: Opiates administered therapeutically could have an inhibitory effect on the neuromuscular axis of the gallbladder, and thus contribute to biliary stasis and acalculous cholecystitis. Methods: Intracellular recordings were made from gallbladder neurons and smooth muscle, and tension measurements were made from muscle strips. Opioid receptor-specific agonists tested: delta, DPDPE; kappa, U-50488H; and mu, DAMGO. Results: Opioid agonists had no effect on gallbladder neurons or smooth muscle. Each of the opioid agonists potently suppressed the fast excitatory synaptic input to gallbladder neurons, in a concentration-dependent manner with half-maximal effective concentration values of about 1 pmol/L. Also, each agonist caused a concentration-dependent reduction in the amplitude of the neurogenic contractile response (halfmaximal effective concentration values: DPDPE, 189 pmol/L; U-50488H, 472 pmol/L; and DAMGO, 112 pmol/L). These ganglionic and neuromuscular effects were attenuated by the highly selective opioid-receptor antagonist, naloxone. Opioid-receptor activation also inhibited the presynaptic facilitory effect of cholecystokinin in gallbladder ganglia. Immunohistochemistry with opioid receptor-specific antisera revealed immunostaining for all 3 receptor subtypes in nerve bundles and neuronal cell bodies within the gallbladder, whereas opiate-immunoreactive nerve fibers are sparse in the gallbladder. Conclusions: These results show that opiates can cause presynaptic inhibition of excitatory neurotransmission at 2 sites within the wall of the gallbladder: vagal preganglionic terminals in ganglia and neuromuscular nerve terminals. These findings support the concept that opiates can contribute to gallbladder stasis by inhibiting ganglionic activity and neurogenic contractions.
Peptides, 2012
In isolated guinea-pig ileum (GPI), the -opioid acute withdrawal response is under the control of several neuronal signaling systems, including the -opioid, the A 1 -adenosine and the CB 1 receptors, which are involved in the inhibitory control of the -withdrawal response. After -opioid system stimulation, indirect activation of -opioid, A 1 -adenosine and CB 1 systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated whether the NOP system is also involved in the regulation of the acute -withdrawal response. Interestingly, we found that in GPI preparation, the NOP system is not indirectly activated by the -opioid receptor stimulation, but instead this system is able by itself to directly regulate the acute -withdrawal response. Specifically, our results clearly highlight first the existence of an endogenous tone of the NOP system in GPI, and second that it behaves as a functional anti-opioid system. We also found that, the NOP receptor system is involved in the regulation of the CCk-8-induced contracture intensity, only when in the presence of the -opioid receptor stimulation. This effect seems to be regulated by an activation threshold mechanism. In conclusion, the NOP system could act as neuromodulatory system, whose action is strictly related to the modulation of both excitatory and inhibitory neurotransmitters released in GPI enteric nervous system. (P. Marini). 1 These authors contributed equally to this study. has also been shown to exert an inverse effect on morphineinduced adverse actions, such as tolerance, reward, and impairment of learning and memory. Therefore, the -opioid receptor has received much attention in the effort to develop alternative analgesics to -opioid receptor agonists and agents for the treatment of drug addiction. However, the activation of the -opioid receptor also produces several undesirable side effects such as dysphoria, water diuresis, salivation, emesis, and sedation in non-human primates, which may limit the clinical utility of -opioid receptor agonists for pain and drug abuse treatment .