The inhibition of tail-pinch-induced food intake by cholecystokinin octapeptides and their fragments

doi:10.1016/0024-3205(84)90135-8

Life Sciences

Volume 35, Issue 2, 9 July 1984, Pages 163-170

https://doi.org/10.1016/0024-3205(84)90135-8 Get rights and content

Abstract

The effects of intraperitoneally (ip.) and intracerebroventricularly (icv.) administered sulfated and nonsulfated cholecystokinin octapeptide (CCK-8-SE and CCK-8-NS) and their N- and C-terminal fragments on the tail-pinch-induced feeding behavior of rats were investigated. After ip. administration, only CCK-8-SE inhibited tail-pinch-induced food intake. After icv. administration, both CCK-8-SE and CCK-8-NS, in doses of 800 pmole/rat, reduced the amount of food eaten. Of the CCK fragments tested icv., the sulfated N-terminal fragments, the middle portion of the CCK-8-sequence (the CCK-3-6 fragment), and the C-terminal tetrapeptide depressed the food intake of rats during tail-pinch, whereas the C-terminal tripeptide significantly increased it. The results suggest that CCK peptides inhibit tail-pinch-induced feeding by separate mechanisms, depending on the route of administration.

References (28)

S.M. Antelman et al.
Brain Res.
(1975)
A.S. Levine et al.
Reg. Peptides
(1981)
J.E. Morley et al.
Life Sci.
(1980)
J.E. Morley et al.
Eur. J. Pharmacol.
(1980)
A.S. Levine et al.
Brain Res.
(1981)
J.E. Morley et al.
Brain Res.
(1981)
J.E. Morley et al.
Physiol. Behav.
(1981)
M. Fekete et al.
Peptides
(1981)
J.E. Morley et al.
Life Sci.
(1981)
J.E. Morley
Life Sci.
(1982)

D.M. Lorenz et al.

Physiol. Behav.

(1979)

G. Telegdy et al.

Advances in Pharmacological Research and Practice. Vol. VII. Aminergic and Peptidergic Receptors

M. Fekete et al.

Neurochemistry Intern.

(1981)

T. Kádár et al.

Neuropharmacology

(1983)

Cited by (9)

Neuropeptides and the central regulation of body temperature during fever and hibernation
1990, Journal of Thermal Biology
Neuropeptides, acting on structures within the central nervous system influence body temperature. Non-opioid peptides induce hypothermia usually, while opioid peptides are mostly hyperthermic. Neuropeptides exert their effect only when injected into specific brain areas.
Hypo- Or hyperthermic effect of neuropeptides may be either due to changes in threshold body temperatures for induction of thermoregulatory effectors or due to changes in hypothalamic thermosensitivity.
At the cellular level the opioid peptides also act differently than the non-opioid peptides. The opioid peptides mostly inhibit spontaneous neuronal firing, while the non-opioid peptides usually stimulate it. Neuropeptides exert their influence on all neurones in the hypothalamus, independently on their temperature characteristics.
Neuropeptides may play a role in the regulation of body temperature under stressful conditions and during fever or hibernation, in particular. Some neuropeptides, namely AVP, α-MSH and ACTH, act as natural antipyretic substances by lowering the threshold for cold thermogenesis.
Neuropeptides also modulate food intake, reproduction and many other functions which are substantially changed during hibernation. There appears to be a correlation between the effect of peptides on the control of food intake and on the control of body temperature. Opioid peptides, which increase food intake, induce hyperthermia, while non-opioid peptides, which are appetite inhibiting, induce hypothermia. The exact role o neuropeptides in the regulation of body temperature, food intake and gonadal activity of hibernators remains unclear, however.
Inhibition of feeding by the C-terminal tetrapeptide fragment of cholecystokinin in a novel environment
1986, Neuropeptides
Several doses of the C-terminal tetrapeptide fragment of cholecystokinin octapeptide (CCK-5–8) were injected intraperitoneally (ip.) and intracerebroventricularly (icv.), and their effects on the feeding of 24-hr food-deprived rats in familiar and novel environments were studied. In the familiar environment, CCK-5–8 ip. or icv. had no effect on the food intake of the rats. In the novel environment (i.e. in an open field), CCK-5–8 showed merely slight effects on the main open-field parameters: only ip. administered CCK-5–8 enhanced the incidence of grooming. Of the feeding parameters tested in the open field, mainly the food intake/approach to food ratio was depressed by CCK-5–8 ip. or icv. The 24 μmole/kg ip. dose of CCK-5–8 decreased the food intake, while the 8 pmole icv. dose increased the number of approaches to food. After the treatments found to be the most effective, the latency to first bite was also enhanced. The results suggest that CCK-5–8 can amplify the arousal enhancement elicited by novelty through a central mechanism.
Administered peptides inhibit the degradation of endogenous peptides. The dilemma of distinguishing direct from indirect effects
1985, Peptides
Virtually all peptides are biologically active following central administration as a consequence of both direct and indirect cellular actions. Direct effects are mainly interactions with specific membrane receptors but may include unions with other components of the receptor/effector complex. Significant indirect biological effects of exogenous peptides, including apparent secretagogue effects on endogenous peptides largely overlooked in practice, result from extensive competition with endogenous peptides for degradative enzymes (peptidases). A consequence of this competition is enhancement of tonic or intermittent activity of endogenous peptides. The pharmacological profile of any peptide reflects or includes, therefore, the spectrum of endogenous peptides that is protected from peptidase action. It is likely that certain pharmacologically active peptides, including a large number of di-, tri- and oligo-peptides, elicit responses mainly or exclusively by competing for peptidases. Therefore, reliable estimates of the relative contributions of direct and indirect actions of exogenous peptides may be difficult, if not impossible, to obtain.
Peptides as central regulators of feeding
1985, Brain Research Bulletin
During the past decade there has been an increased awareness of the role peptides play as neuromodulators. In this article we review the available data on peptides as central regulators of food ingestion. We stress the possible problems of non-specific effects. We stress that whereas many peptides decrease feeding after central injection, only two families of peptides have been shown to increase feeding after central injection. These are the opioid family and the pancreatic polypeptide-neuropeptide Y family. The putative role of corticotropin releasing factor as the mediator of norepinephrine and serotonin effects on feeding is discussed.
Peptides and feeding
1985, Peptides
This report reviews the hypothesis that peptides play a role in appetite modulation, stressing that the available evidence is predominantly pharmacological and thus caution needs to be taken in assigning physiological significance at this time. Two peptide systems have been postulated—a peripheral satiety system, typified by the gastrointestinal hormone cholecystokinin and a central feeding system driven by the opioid peptides and neuropeptide Y. This review also discusses the putative role of peptides in (1) the anorexia of aging, (2) drinking elicited by feeding and (3) as mediators of the autonomic effects seen in association with ventromedial hypothalamic lesions.
Peptidergic Regulation of Feeding
1985, International Review of Neurobiology
This chapter focuses on the role of peptides as the regulators of food intake. Peptides, besides acting as neurotransmitters within the central nervous system, can also be released into the bloodstream and circulate, thereby acting as classical hormones. In addition, peptides can be released from nonneuronal cells in the periphery and produce an effect on neighboring cells, which is the so-called paracrine system. It would appear that all three of these modes of action of peptides are involved in the regulation of food intake. To understand the interactions of the multiple neurotransmitters involved in the regulation of feeding, a hypothetical model utilizing a matchstick diagram, from which further experiments can be designed to probe the mysteries of appetite regulation, was developed. The model originally proposed that the hypothalamus acts as a neuroendocrine transducer with the control of food intake involving a balance between a number of neuropeptides and monoamines.

View all citing articles on Scopus

View full text

The inhibition of tail-pinch-induced food intake by cholecystokinin octapeptides and their fragments

Abstract

Brain Res.

Reg. Peptides

Life Sci.

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Physiol. Behav.

Peptides

Life Sci.

Life Sci.

Physiol. Behav.

Neurochemistry Intern.

Neuropharmacology