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L Nunan

Publications and source records attributed to L Nunan.

At least 19 recordsLinked to original sources
PubMed1992

Chimeric M1/M2 muscarinic receptors: correlation of ligand selectivity and functional coupling with structural modifications.

Chimeric M1/M2 receptors were expressed in murine fibroblasts (B82) transfected with recombinant m1/m2 receptor genes. The binding affinities of a number of muscarinic antagonists and the agonist carbachol for these chimeric receptors were compared with the ligands' affinities for the M1 and M2 receptors expressed in the B82 cells. The tricyclic compounds, namely pirenzepine (PZ), 11-([2-[(diethylamino)methyl]-1-piperidinyl]acetyl)-5,11- dihydro-6H-pyrido-[2,3-6][1,4]benzodiazepine-6-one (AF-DX 116) and himbacine, shared a binding site between transmembrane domains VI and VII. However, the selective interaction of pirenzepine with M1 and AF-DX 116 and himbacine with M2 involved different structural regions. The high-affinity binding for 4-diphenylacetoxy-N- methylpiperidine and hexahydrosiladifenidol was confined to within loop o2 and transmembrane domains V and VI, which were clearly distinguishable from those of the tricyclic compounds. These results support the hypothesis that the ligands' stereochemical features are critical in their optimal alignment within the ligand binding pocket. The cytoplasmic i3 loop modulated the binding of carbachol such that receptors which contained the i3 domain from the M2 receptor exhibited a single high-affinity state, whereas those with the i3 domain from the M1 receptor had an additional low-affinity state for the agonist. The i3 regions are essential for the differential functional coupling of the M1 and M2 receptors to second messenger systems; however, additional upstream regions seem to be essential for a potent and efficacious activation of phospholipase C by the M1 receptor. This study provides new insight into the molecular basis of ligand selectivity.

Amino Acid Sequence↗
PubMed1989

Differential modulation by [D-Pen2, D-Pen5]enkephalin and dynorphin A-(1-17) of the inhibitory bladder motility effects of selected mu agonists in vivo.

The possibility that the delta agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE) and the putative endogenous kappa agonist, dynorphin A-(1-17) could differentially modulate the effects of a group of chemically diverse mu agonists was evaluated using inhibition of volume-induced contractions of the rat urinary bladder as a model of central nervous system opioid receptor function in vivo. Intracerebroventricular administration of equieffective doses of the mu agonists [D-Ala2, NMPhe4, Gly-ol]enkephalin (DAMGO), [N-MePhe3, D-Pro4]enkephalin (PL017), morphine, normorphine, sufentanil, etorphine, phenazocine, meperidine and methadone inhibited spontaneous bladder contractions for approximately 20 to 30 min. Low doses of DPDPE or dynorphin A-(1-17) failed to affect spontaneous bladder contractions; higher doses of DPDPE (greater than 15.5 nmol) and dynorphin A-(1-17) (i.e., greater than 3.7 nmol), inhibited bladder contractions. When coadministered i.c.v., DPDPE displaced the morphine dose-response line to the left and also potentiated the effects of normorphine and etorphine. In contrast, DPDPE failed to alter the actions of equieffective doses of DAGO, PL017, meperidine, methadone, phenazocine or sufentanil. The potentiation of the effects of morphine by DPDPE were prevented by i.c.v. coadministration of the delta antagonist, ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH); at the dose tested, the delta antagonist had no agonist effects alone and did not antagonize the effects of morphine directly. Furthermore, the agonist effects of morphine were potentiated by several different doses of DPDPE. Administration of i.c.v. dynorphin A-(1-17) produced a rightward displacement of the morphine dose-response line and also antagonized the effects of normorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1988

U50,488H differentially antagonizes the bladder effects of mu agonists at spinal sites.

The mu antagonist property of the kappa agonist U50,488H was studied at the spinal level, using motility of the rat urinary bladder as an endpoint in vivo. Intrathecal (i.th.) administration of the mu agonists [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAGO), [N-MePhe3,D-Pro4]enkephalin (PL017), morphine and normorphine, as well as the delta agonist [D-Pen2,D-Pen5]enkephalin (DPDPE), resulted in an equieffective inhibition of volume-initiated contractions of the urinary bladder. In contrast, i.th. administration of U50,488H, a highly selective kappa agonist, had no effect on bladder motility. Pretreatment of rats with i.th. U50,488H prior to agonist administration, blocked the suppression of spontaneous bladder activity induced by equieffective i.th. does of morphine and normorphine, but failed to alter the inhibitory effect of the mu agonists DAGO and PL017, or that of the delta agonist DPDPE. The finding that U50,488H differentially antagonized the identical bladder effects of several mu agonists suggests the presence of mu receptor subtypes (mu isoreceptors) in the rat spinal cord, which may be involved in the regulation of bladder function.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Naloxonazine and opioid-induced inhibition of reflex urinary bladder contractions.

Spontaneous volume-induced contractions of the urinary bladder were recorded isometrically in urethane-anesthetized rats. Contractions were inhibited by alternate submaximal but equieffective doses of the selective mu and delta-opioid ligands [D-Ala2-Me-Phe4,Gly(ol)5] enkephaline (DAGO) and [2-D-penicillamine, 5-D-penicillamine] enkephalin (DPDPE), respectively, administered by the intracerebroventricular (i.c.v.) or spinal intrathecal (i.t.) route. Naloxonazine, postulated to be an irreversible mu 1-opioid receptor antagonist, administered by the same route, antagonized the effects of both DAGO and DPDPE. The antagonism of the effect of DAGO was reversed 3-4 hr later but that of DPDPE was more prolonged. Recovery of the effect of DPDPE was observed some 24 hr later. A similar pattern of activity against DAGO and DPDPE given intraventricularly or intrathecally was observed following intravenous injection of naloxonazine (10 mg/kg). Also naloxonazine (i.c.v., i.t. or i.v.) antagonized the effect of morphine given intraventricularly or intrathecally, but antagonism was not observed when morphine was retested 3-4 hr and 24 hr later. Naloxonazine increased the frequency of contraction of the bladder after each route of administration. This effect lasted 1-3 hr and was not seen 24 hr later. Systemic administration of naloxone (10 mg/kg, i.v) also increased the frequency of bladder contraction and attenuated or abolished the effect of DAGO given intraventricularly or intrathecally and the delta-receptor agonist [2-D-penicillamine, 5-L-penicillamine] enkephaline (DPLPE).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mu and delta opioid ligands inhibit reflex contractions of the urinary bladder in the rat by different central mechanisms.

The supraspinal and spinal mechanisms of opioid-induced inhibition of reflex contractions of the urinary bladder were studied in female rats, anesthetized with urethane. A variety of central manipulations was made to distinguish the effects produced by [D-Ala2-Me-Phe4-Gly(ol)5]-enkephalin (DAGO), a selective mu-opioid receptor ligand, from those of the delta ligand [2-D-penicillamine, 5-L-penicillamine]-enkephalin (DPLPE), administered by either intracerebroventricular (i.c.v.) or by spinal intrathecal (i.t.) injection. The effect of intraventricular but not of intrathecal administration of DPLPE was abolished 4-5 hr after the systemic administration of reserpine (5 mg/kg, i.p.). Reserpine did not modify the actions of DAGO, given by either route. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 200 micrograms, i.c.v.) attenuated the effect of DPLPE given intraventricularly but not when given intrathecally, measured 7 days later. The effect produced by DPLPE given by either route was unchanged by pretreatment with 6-hydroxydopamine (6-OHDA, 150 micrograms i.c.v.). Neither 5,7-DHT nor 6-OHDA altered the effect of administrations of DAGO. The effect of DPLPE given intraventricularly was attenuated or abolished, in a dose-related and reversible manner, following the administration of naloxone or methysergide intrathecally but not by phentolamine, propranolol or atropine. The effect of DAGO given intraventricularly was antagonised by naloxone but not by any of the other antagonists. These observations suggested that the supraspinally- and spinally-mediated inhibition of reflex contractions of the urinary bladder produced by mu or delta receptor ligands can be dissociated. The supraspinal effect of DPLPE involved a descending serotoninergic, but not adrenergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Supraspinal and spinal mechanisms in morphine-induced inhibition of reflex urinary bladder contractions in the rat.

The supraspinal and spinal mechanisms of morphine-induced inhibition of isometrically recorded reflex urinary bladder contractions were studied in rats anesthetized with urethan. Chronic intracerebroventricular administration of 5,7-dihydroxytryptamine (200 micrograms) or 6-hydroxydopamine (150 micrograms), to selectively deplete central serotoninergic and noradrenergic systems, attenuated the intracerebroventricular effect but not the intrathecal effect of morphine. The intracerebroventricular effect of morphine was reversibly attenuated or abolished by an intrathecal injection of the novel delta-receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Arb-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) (1-3 micrograms) and by intrathecal methysergide (4-10 micrograms), phentolamine (5-10 micrograms), and yohimbine (5-10 micrograms) but not by intrathecal propranolol (10 micrograms), atropine (8 micrograms) or saline (2 micrograms) administered at similar molar concentrations and volumes respectively. These observations support the hypothesis that supraspinal and spinal mechanisms involved in morphine-induced inhibition of reflex urinary bladder contractions can be dissociated. The supraspinal actions of morphine were mediated indirectly via descending 5-hydroxytryptamine and noradrenergic pathways which activated specific 5-hydroxytryptamine and alpha-adrenergic but not beta-adrenergic receptor in the spinal cord. In addition, supraspinal morphine indirectly activated a spinal opioid system which could be directly activated by intrathecal morphine. The similarities between these observations and studies of central pathways mediating nociception and opioid analgesia suggest that similar physiological mechanisms control certain somatic and visceral activity.

Animals↗
PubMed1987

Mu antagonist properties of kappa agonists in a model of rat urinary bladder motility in vivo.

The possibility that the kappa agonists, U50,488H, ethylketazocine and tifluadom, might act as opioid antagonists was studied using the inhibition of the anesthetized rat micturition reflex in vivo as a pharmacological endpoint. Intracerebroventricular administration of equieffective doses of the mu agonists [D-Ala2, NMePhe4, Gly-ol]enkephalin (0.01 nmol), [N-MePhe3, D-Pro4]enkephalin (0.03 nmol), morphine (0.08 nmol), normorphine (0.3 nmol), sufentanil (0.002 nmol), etorphine (0.004 nmol), phenazocine (17 nmol) and meperidine (176 nmol) inhibited spontaneous bladder contractions for a duration of approximately 20 to 30 min. Similarly, i.c.v. administration of the delta-selective agonist (D-Pen2, D-Pen5]enkephalin (15 nmol) inhibited the micturition reflex for approximately the same duration. The kappa agonists U50,488H (22 nmol), ethylketazocine (3 nmol) and tifluadom (3 nmol) did not alter bladder activity after i.c.v. administration. Higher doses of ethylketazocine (10 nmol) or tifluadom (20 nmol), but not U50,488H, produced consistent suppression of bladder contractions. Pretreatment of rats (-15 min, i.c.v.) with doses of U50,488H, ethylketazocine or tifluadom which did not produce an agonist effect consistently blocked the inhibitory actions of the mu agonists morphine and normorphine on bladder motility, but failed to antagonize the similar actions of the mu agonists [D-Ala2, NMePhe4, Gly-ol]enkephalin, [N-MePhe3, D-Pro4]enkephalin, phenazocine, meperidine or those of the delta agonist [D-Pen2, D-Pen5]enkephalin. Centrally initiated bladder effects of the mu agonists etorphine and sufentanil were antagonized by U50,488H but unaffected by ethylketazocine or tifluadom. In addition, administration of U50,488H (i.c.v.) during a morphine-induced bladder shutdown resulted in either an immediate recovery of bladder activity or a shortened duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Centrally administered beta-endorphin produces prolonged changes in delta-opioid ligand activity in vivo.

Spontaneous reflex bladder contractions were recorded isometrically in urethane anesthetized rats. Bladder contractions were depressed by intracerebroventricular injections of the mu-opioid receptor agonist [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO) and the delta-agonist [2D-penicillamine,5D-penicillamine]enkephalin (DPDPE) respectively. The effect of DPDPE was selectively antagonized by ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH; Aib = alpha-aminoisobutyric acid). However following the administration of beta-endorphin the antagonistic action of ICI 174,864 could no longer be observed. In addition ICI 174,864 exhibited agonistic activity following beta-endorphin and the effects of DPDPE were prolonged in a dose related manner by beta-endorphin. These observations suggest that beta-endorphin may produce complex changes in central delta-opioid receptor activity.

Animals↗
PubMed1986

Meptazinol: unusual in vivo opioid receptor activity at supraspinal and spinal sites.

Systemic (1-10 mg/kg, s.c.), intracerebroventricular (i.c.v. 20-80 micrograms) and spinal intrathecal (i.t., 5-20 micrograms) administration of meptazinol hydrochloride produced dose-related inhibition of reflex contractions of the urinary bladder, recorded isometrically in urethane-anesthetized rats. The effects of meptazinol were reversed by naloxone administered by the same route. Indeed, this was achieved with intracerebroventricular or intrathecal administration of naloxone (2 micrograms), which also selectively antagonized the mu-receptor ligand [D-Ala2, MePhe4, Gly(ol)5]enkephalin (DAGO). However ICI 174,864 (3 micrograms, i.c.v. or i.t.), a delta-opioid receptor antagonist, did not affect the actions of meptazinol given intracerebroventricularly or intrathecally though it consistently abolished the equieffective actions of a selective delta-receptor ligand (2-D-penicillamine, 5-L-penicillamine) enkephalin (DPLPE). Naloxonazine (5 micrograms, i.c.v. or i.t.), an irreversible mu 1-opioid receptor antagonist, produced prolonged antagonism of the effects of DPLPE and meptazinol. The effects of DPLPE partially or completely recovered by 24 hr, indicating that naloxonazine produced prolonged antagonism of delta-opioid receptors. The effects of maptazinol however only recovered after 72 hr, suggesting that antagonism by naloxonazine of this ligand was irreversible and was mediated through a unique opioid receptor interaction. Subthreshold doses of meptazinol (10 micrograms, i.c.v.; 3 micrograms, i.t.) consistently antagonized the effects of morphine given intracerebroventricularly or intrathecally but not the equieffective doses of DPLPE or DAGO. These observations suggest that meptazinol inhibited reflex contractions of the bladder by supraspinal and spinal mu-opioid receptor activation. Furthermore, its agonistic effect and its antagonistic actions were compatible with interactions at a subpopulation of opioid receptors, possibly mu 1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Opioid inhibition of reflex urinary bladder contractions: dissociation of supraspinal and spinal mechanisms.

The supraspinal and spinal mechanisms of morphine induced inhibition of reflex urinary bladder contractions were studied in the urethane anesthetized rat. The inhibition of bladder contractions by intracerebroventricular (i.c.v.) morphine was abolished by intrathecal (i.t.) naloxone. In addition systemic reserpine (3.5-5.0 mg/kg, i.p.) abolished the inhibitory effect of both systemic morphine and i.c.v. morphine but not that of i.t. morphine. These data support the involvement of separate supraspinal and spinal mechanisms in the effects of morphine on bladder motility. The supraspinal effect appeared to be mediated indirectly via a monoaminergic system whereas the spinal action was mediated independently of monoamines. However, both the indirect supraspinal and the direct spinal mechanism involved a spinal naloxone-sensitive process possibly an endogenous enkephalinergic system.

Animals↗
PubMed1985

Prolonged in vivo antagonism of central mu- and delta-opioid receptor activity by beta-funal trexamine.

beta-Funaltrexamine (beta-FNA) was tested in the spinal cord and supraspinally against inhibition of reflex bladder contractions produced in the anesthetized rat by the opioid-receptor selective agonists [D-Ala2, MePhe4, Gly (ol)5]enkephalin (DAGO, mu-agonist) and [D-Pen2, D-Pen5] enkephalin (DPDPE, delta-agonist). All agents were microinjected either intracerebroventricularly (i.c.v.) or intrathecally (i.t.). beta-FNA (1-8 micrograms) produced long-lasting antagonism of both DAGO and DPDPE. Complete recovery from its effects was only observed some 24-32 h later. Higher doses of beta-FNA (4 and 8 micrograms i.t.) produced short-lived agonistic activity though the selectivity of this was not determined. It was concluded that beta-FNA was a potent, long-lasting antagonist at central opioid receptors in vivo but was unselective for the mu and delta opioid receptor.

Animals↗
PubMed1985

Central delta-opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat.

The in vivo effects of a number of opioid agonists and antagonists were studied on the spontaneous reflex contractions of the urinary bladder recorded isometrically in the rat anesthetized with urethane. All substances were administered into the central nervous system by the intracereboventricular (i.c.v.) or spinal intrathecal (i.t.) route. The conformationally restricted enkephalin analogues [2-D-penicillamine, 5-L-cysteine] enkephalin (DPLCE), [2-D-penicillamine, 5-L-penicillamine] enkephalin (DPLPE) and [2-D-penicillamine, 5-D-penicillamine] enkephalin (DPDPE) produced dose-related inhibition of reflex bladder contractions when administered by the i.c.v. or i.t. route. Both the novel delta-opioid receptor antagonist ICI 154,129 (200-600 micrograms) [N,N-bisallyl-Tyr-Gly-Gly-Psi-(CH2S)-Phe-Leu-OH) and ICI 174,864 (1-3 micrograms) [N,N-dially-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid] attenuated or abolished the effects of DPLCE, DPLPE and DPDPE when administered by the i.c.v. or i.t. route. The antagonism observed was selective since the equipotent inhibition produced by the mu-opioid receptor agonist [D-Ala2, Me-Phe4, Gly(ol)5] enkephalin (DAGO) was unaffected. Overall, ICI 154,129 was considerably weaker than ICI 174,864 and both antagonists inhibited bladder activity at doses higher than those required to demonstrate delta-receptor antagonism. Further studies of the agonistic effect of ICI 174,864 showed that it was insensitive to low doses of naloxone (2 micrograms, i.c.v. or i.t.) but could be abolished by higher (10-15 micrograms) doses of naloxone. These observations suggested that the agonistic effect of ICI 174,864 was not mediated by mu-opioid receptor. beta-Endorphin (0.2-1.0 micrograms, i.c.v.) inhibited bladder contractions but following recovery from this effect, appeared to prevent the expression of delta-receptor antagonism by ICI 174,864. In addition a previously subthreshold dose of ICI 174,864 now exhibited marked agonistic activity. The inhibitory effect of a submaximal dose of DPDPE was also potentiated by beta-endorphin under these circumstances. These observations suggest that supra-spinal and spinal delta-opioid receptors are involved in the opioid-mediated inhibition of reflex bladder contractions in the rat. Moreover beta-endorphin may be important in regulating central delta-opioid receptors.

Animals↗
PubMed1985

Proenkephalin A fragments exhibit spinal and supraspinal opioid activity in vivo.

The inhibition of reflex urinary bladder contractions, recorded isometrically in the urethane-anesthesized rat, was used as an index of central opioid activity. Inhibition of bladder activity has been shown to be mediated both spinally and supraspinally by mu and delta opioid receptors. Using this model a number of neuropeptide fragments of the proenkephalin A molecule (peptide F, peptide E, BAM 22P, BAM 12P, Met5-enkephalin-Arg6,Phe7,Leu8, Met5-enkephalin-Arg6,Phe7, Met-enkephalin, Leu-enkephalin) were tested for in vivo activity. Each of the fragments inhibited reflex bladder contractions when administered by bolus microinjection into a lateral ventricle (i.c.v.) or intrathecally into the spinal subarachnoid space (between L3 and L4 vertebra). The larger molecular weight peptides produced more prolonged inhibition of bladder activity than the smaller molecular weight ones, with the rank order of activity being similar at spinal and supraspinal sites: peptide F greater than or equal to peptide E = BAM 22P greater than BAM 12P greater than Met5-enkephalin-Arg6,Phe7,Leu8 = Met5-enkephalin-Arg6,Phe7 greater than or equal to Met-enkephalin = Leu-enkephalin. The relative receptor selectivity of each fragment was further determined using the opioid antagonists naloxone (mu receptors) and ICI 174,864 (N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) (delta receptors). The activity (Ke) of each antagonist against equieffective doses of the highly selective opioid receptor ligands [D-Ala2,Me-Phe4,Gly(ol)5]enkephalin (mu receptors) and [D-Pen2,D-Pen5]enkephalin (delta receptors) was compared with that against the proenkephalin A fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evidence that naloxonazine produces prolonged antagonism of central delta opioid receptor activity in vivo.

Intracerebroventricular (i.c.v.) administrations of the postulated mu 1 opioid receptor antagonist naloxonazine produced an increase in the frequency of urinary bladder contractions recorded isometrically in the anesthetized rat. This substance also antagonized the inhibition of spontaneous bladder contractions produced by submaximal i.c.v. doses of the highly selective mu opioid agonist [D-Ala2-MePhe4,Gly-(ol)5]enkephalin (DAGO) and the delta opioid agonist [D-Pen2,D-Pen5]enkephalin (DPDPE). The antagonism of DAGO was reversible but that of DPDPE lasted up to 30 h. These data suggest that endogenous opioids are involved in the central control of bladder motility and that naloxonazine is a long-lasting delta opioid receptor antagonist.

Animals↗
PubMedDate not supplied

Selective delta-opioid receptor antagonism by ICI 174,864 in the central nervous system.

The effects of the novel gamma-opioid receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) have been examined in the CNS in vivo using spontaneous reflex contractions of the rat urinary bladder as an index of activity. Bladder contractions were inhibited by equipotent intracerebroventricular (ICV) doses of the selective mu-agonist DAGO [D-Ala2, MePhe4,Gly-(ol)5]enkephalin and the delta-agonist DPDPE[D-Pen2, D-Pen5]enkephalin. ICI 174,864 (1-3 micrograms) administered by the same route produce a selective and reversible antagonism of DPDPE effects. At higher doses (6-15 micrograms, ICV) ICI 174,864 exhibited marked agonistic activity, producing inhibition of bladder contractions that were resistant to ICV naloxone (1-2 micrograms). Thus ICI 174,864 was considered a selective central delta-opioid receptor antagonist but its usefulness was limited by additional agonistic properties.

Animals↗
PubMedDate not supplied

Neuropeptide Y depresses reflex urinary bladder contractions in rats and modifies central activity of opioid agonists.

The 36 amino acid peptide neuropeptide Y (NPY) has been found distributed in central structures associated with nociception and the actions of opioid analgesics. We therefore studied its central actions on reflex bladder contractions which we have shown to be inhibited by supraspinal and spinal opioid administrations in urethane anesthetized rats. Neuropeptide Y produced a dose related (0.5-2 micrograms per rat) inhibition of bladder contractions following intracerebroventricular (ICV) and spinal intrathecal (IT) administrations. These effects could not be antagonized by naloxone (2 micrograms, ICV or IT) or by ICI 174,864 [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid] (3 micrograms, ICV or IT). NPY (0.5-1 micrograms) reduced the ICV and IT effects of morphine but potentiated the action of the selective delta-receptor ligand [2-D-penicillamine, 5-L-penicillamine] enkephalin (DPLPE). The effect of the mu-selective opioid ligand [D-Ala2, Me-Phe4, Gly(ol)5] enkephalin (DAGO) were unaffected as were the submaximal ICV and IT actions of noradrenaline. It was concluded that NPY-induced inhibition of bladder activity was not due to a direct opioid receptor interaction. However since NPY consistently changed the activity of opioids (morphine and DPLPE), this suggested a possible physiological role in the regulation of opioid receptors, central neural excitability and thereby visceral activity.

Animals↗