Opioid receptor binding properties of analgesic analogues of cholecystokinin oceapeptide

Slaninová, Jiřina; Knapp, Richard J.; Wu, Jing; Fang, Sunan; Kramer, Thomas H.; Burks, Thomas F.; Hruby, Victor J.; Yamamura, Henry I.

doi:10.1016/0014-2999(91)90688-m

Cited by 38 publications

(25 citation statements)

References 7 publications

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“…A similar effect has previously been shown with other cholecystokinin peptides (Jura & Zetler 1981;Barbaz et al 1986;Slaninova et al 1991;. The obtained results are also in agreement with our previous study that caerulein induces antinociception in hot-plate tests (Zarrindast et al 1997), although other reports have indicated that cholecystokinin does not alter pain response in the tail-flick test (Moran et al 1986;Dourish et al 1988;O'Neill 1989).…”

Section: Discussionsupporting

confidence: 82%

Role of Cholecystokinin Receptors in Induction of Antinociception in Hot‐Plate Test

Rezayat

Rahnavard

Zarrindast³

2000

Pharmacology & Toxicology

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In the present study, the antinociceptive effect of cholecystokinin receptor agonists in the hot-plate test in mice has been evaluated. Subcutaneous administration of cholecystokinin octapeptide (cholecystokinin-8; 0.001, 0.005, 0.01, 0.05, and 0.1 mg/kg), unsulfated cholecystokinin octapeptide (cholecystokinin-8U; 0.1 mg/kg) or caerulein (0.25 mg/kg) produced antinociception. Administration of the cholecystokinin tetrapeptide (cholecystokinin-4; 0.25, 0.5 and 1.0 mg/ kg) had no effect in the hot-plate test. Subcutaneous injection of the selective cholecystokinin receptor antagonists, MK-329 (0.125, 0.25 and 0.5 mg/kg) or L-365,260 (0.125, 0.25 and 0.5 mg/kg), produced no antinociceptive response. When the animals were pretreated with the cholecystokinin receptor antagonists or naloxone (0.5 and 1 mg/kg), a significant decrease in the antinociceptive response induced by cholecystokinin-8 and caerulein was obtained. The results indicate that single administration of cholecystokinin receptor agonists could produce an antinociceptive effect which is probably mediated via cholecystokinin receptors. With respect to the results obtained from morphine and naloxone administration, it is concluded that there may be an interaction between cholecystokinin and opiate mechanisms.The peptide, cholecystokinin, is found in the mammalian nervous system (Vanderhaeghen et al. 1975;Rehfeld 1978;Faris et al. 1983). Caerulein is closely related to the naturally occurring cholecystokinin-8 (Rehfeld & Hansen 1984;Baber et al. 1989). Cholecystokinin-8 and related peptides produce several neural-mediated effects after both peripheral and central administration (Zelter 1982;Baber et al. 1989). Cholecystokinin-like immunoreactivity has been described in areas of the spinal cord and brain which are believed to play a role in nociception. Sulfated cholecystokinin-8 and the small amounts of cholecystokinin-4 are thought to be present in many regions of the midbrain including the periaqueductal gray and substantia nigra, which are important areas in pain modulation (Baber et al. 1989). Exogenously applied cholecystokinin-8 and related peptides have produced different results on pain modulation in rodents (Wiesenfeld-Hallin et al. 1990). Cholecystokinin-8 has been found to reduce the analgesic effect of the morphine and b-endorphin (Itoh et al. 1982). Our previous results also show that pretreatment of mice with cholecystokinin receptor agonist (Cesselin 1995) decreased or increased the morphine-induced antinociception depending on pretreatment time . There is also evidence indicating that the cholecystokinin mechanism may play an important role in pain transmission by modulating CNS opiate mechanisms (Jurna & Zetler 1981;Suh et al. 1992). It has also been suggested that there may be multiple 1986). The highly selective and potent cholecystokinin-A receptor antagonists, MK-329 and L-365,260 are now available, which opens the possibility to evaluate the role of cholecystokinin receptor types in mechanism of pain system (Wiesenfeld-Hal...

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Section: Discussionsupporting

confidence: 82%

Role of Cholecystokinin Receptors in Induction of Antinociception in Hot‐Plate Test

Rezayat

Rahnavard

Zarrindast³

2000

Pharmacology & Toxicology

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“…It has been suggested that activation of CCKB receptors suppresses the binding of selective mu and kappa, but not delta, opioid agonists to their respective receptors through an allosteric interaction [99]. However other studies have failed to find any modification of opioid binding by CCK [100]. Another proposal is that CCK is capable of mobilizing calcium from intracellular stores via post-receptor mechanisms, which opposes the opioid-mediated suppression of internal calcium produced by mu and kappa, but not delta opioid agonists [101].…”

Section: Cholecystokinin As a Factor In The Enhanced Potency Of Morphmentioning

confidence: 97%

Spinal opioid systems in inflammation

Stanfa

Dickenson

1995

Inflamm Res

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Until recently, basic science studies, both behavioural and electrophysiological, have concentrated on the antinociceptive actions of opioids primarily gauged against acute nociceptive responses. However, of more relevance to clinical situations are the actions of opioids in more persistent/prolonged pain states. This review sets out to examine the central actions of opioids against nociception of inflammatory origins. The first section deals with the response of the endogenous opioid system to the development of an inflammatory state and the second examines the ability of exogenous opioids to modulate inflammatory nociception. There are complex changes in the roles of endogenous opioids, in particular dynorphin, at the spinal level after inflammation although the physiological consequences remain unclear. With regard to exogenous opioids, the effectiveness of spinal morphine is rapidly enhanced after inflammation, likely to be due to changes in the interaction between the peptide cholecystokinin and the mu opioid receptor. The ability of inflammatory processes to alter both endogenous opioids and morphine analgesia at the spinal level illustrates the considerable degree of plasticity observed in opioid function.

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“…The novel concept of designing dual-pharmacophore molecules has been successfully developed in our group mainly with the analgesic peptides targeting to both δ/μ opioid receptors and cholecystokinin (CCK) receptors. [17][18][19][20] To date, some molecules are already reported to have both δ/μ opioid agonist and substance P antagonist activities. 21-23 However, their activities are biased for one of the receptors, and no molecule had sufficient and balanced activities for both of opioid and NK1 receptors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Bifunctional C-Terminal-Modified Peptides for δ/μ Opioid Receptor Agonists and Neurokinin-1 Receptor Antagonists

et al. 2007

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A series of bifunctional peptides that act as agonists for δ and μ opioid receptors with δ selectivity and as antagonist for neurokinin-1 (NK1) receptors were designed and synthesized for potential application as analgesics in various pain states. The peptides were characterized using radioligand binding assays and functional assays using cell membrane and animal tissue. Optimization was performed on the fifth residue which serves as an address moiety for both receptor recognitions. It had critical effects on both activities at δ/μ opioid receptors and NK1 receptors. Among the synthesized peptides, H-Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF 3 ) 2 (5) and H-Tyr-DAla-Gly-Phe-Nle-Pro-Leu-Trp-O-3,5-Bzl(CF 3 ) 2 (7) had excellent agonist activity for both δ opioid and μ opioid receptors and excellent antagonist activity for NK1 receptors. These results indicate that the rational design of multifunctional ligands with opioid agonist and neurokinin-1 antagonist activities can be accomplished and may provide a new tool for treatment of chronic and several pain states.

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Opioid receptor binding properties of analgesic analogues of cholecystokinin oceapeptide

Cited by 38 publications

References 7 publications

Role of Cholecystokinin Receptors in Induction of Antinociception in Hot‐Plate Test

Role of Cholecystokinin Receptors in Induction of Antinociception in Hot‐Plate Test

Spinal opioid systems in inflammation

Design, Synthesis, and Biological Evaluation of Novel Bifunctional C-Terminal-Modified Peptides for δ/μ Opioid Receptor Agonists and Neurokinin-1 Receptor Antagonists

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