Evoked Peptide Release

Finally, cannabinoids inhibit the release of neuropeptides like calcitonin gene-related peptide (CGRP), substance P and somatostatin from sensory neurons (Table 4). Capsaicin or electrical stimulation was used to evoke neuropeptide release. In some of these studies, the endocannabinoid anandamide was used, which has a dual effect on neuropeptide release from sensory neurons. Anandamide possesses an inhibitory effect mediated via CBi receptors at low concentrations and... 

Opree A, Kress M (2000). Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia effects on heat-evoked calcitonin gene-related peptide release from rat sicin. /. Neurosci. 20 6289-6293. 

Conversely, the myosuppressins are members of the FLRFamide peptide family, inhibit the spontaneous contractions of the isolated cockroach hindgut, and share the common C-terminal heptapeptide sequence Asp-His-Val-Phe-Leu-Arg-Phe-NHj. They have been isolated from the cockroach L. maderae. locusts Schistocerca gregaria and L. migratoria. and flies Neobellieria bullata and Drosophila melanogaster (1,8,19,20). Leucomyosuppressin (LMS) inhibits evoked transmitter release at the neuromuscular junction of the mealworm Tenebrio molitor (21). 

So far we have discussed the effect of CCK peptides on serotonin brain concentrations. Some evidence also exist on the action of serotonin on the CCK system. Raiteri and colleagues (1993a) looked at the effects of serotonin on the release of cholecystokinin-like immunoreactivity (CCK-LI) in synaptosomes prepared from rat cerebral cortex and nucleus accumbens. In both areas, serotonin increased the calcium-dependent depolarization-evoked CCK-LI release in a dose-related fashion. This effect was antag-... 

The role of peptidergic neurons is not so clear. Capsaicin, the hot chile pepper chemical that evokes release of peptide transmitters from several types of sensory nerves, has been shown to reproduce some of the signs of bronchial hyperreactivity in animal and human experiments. These findings led to the proposal that sensitization of afferent nerve endings played a major role in chronic airway hyperreactivity. However, peptide transmitter antagonists have not been able to prevent bronchoconstriction in several models. Clearly, much remains to be learned about airway pharmacology. 

Fig. 4 Effect of various peptides and nonpeptides on the electrically (3 Hz) evoked tritium overflow from superfused mouse brain cortex slices preincubated with 3H-serotonin. The evoked overflow represents quasi-physiological exocytotic serotonin release. In all experiments, serotonin autoreceptors were blocked by metitepine. The figure shows that human neuropeptide Y concentration-dependently inhibited serotonin release and that this effect was mimicked by human neuropeptide Y (13-36) (NPYi3 36), which has a high affinity for Y2 but a very low affinity for Yi receptors. These results are compatible with the view that neuropeptide Y acts via Y2 receptors in the present model. For the sake of comparison, the figure also shows the inhibitory effects of another three agonists, acting via cannabinoid CBi, histamine H3 and prostaglandin EP3 receptors and used at concentrations causing the maximum or near-maximum effect at their respective receptors. Drug concentrations in pM. P < 0.05, P < 0.003, compared to the control (from Nakazi et al. 2000 and Nakazi 2001 redrawn).

Abrahamsson C (2000) Neuropeptide Y1- and Y2-receptor-mediated cardiovascular effects in the anaesthetized guinea pig, rat, and rabbit. J Cardiovasc Pharmacol 36 451-8 Ackley MA, Hurley RW, Virnich DE et al (2001) A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist. Pain 91 377-88 Aimone LD, Yaksh TL (1989) Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. Peptides 10 1127-31... 

Since the discovery and characterization of P-endorphin (31 amino acids) as an opioid peptide in 1976, the opinion has been widely held that this peptide has a role in the control of pain (Akil et al., 1984 Basbaum and Fields, 1984 Loh et al 1976 Rossier et al., 1977). POMC-derived P-endorphin is considered to be a key component of the endogenous antinociceptive system attenuating the stress- and inflammation-induced hyperalgesia (Rossier et al., 1977 Stein et al., 1990 Sun et al., 2003). It binds with high affinity to both MOR and DOR (Akil et al., 1984). Pain stimulation induces PAG release of 3-endorphin and the ICV administration of 3-endorphin produces analgesia (Akil et al., 1984). Similarly, both spinal and peripheral administration of 3-endorphin evokes antinociceptive effects in different pain models (Chung et al., 1994 Stein et al., 1990 Suh et al., 1994 Suh et al.,... 

Eflington HC, Cotter MA, Cameron NA, Ross RA (2002) The effect of cannabinoids on capsaicin-evoked caldtonin gene-related peptide (CGRP) release from the isolated paw skin of diabetic and non-diabetic rats. Neuropharmacology 42 966-975 Endres-Becker J, HeppenstaU PA, Mousa SA, Labuz D, Oksche A, Schafer M, Stein C, Zollner C (2007) Mu-opioid receptor activation modulates transient receptor potential vanilloid 1... 

E. Nonadrenergic, Noncholinergic (NANC) Transmission Some nerve fibers in autonomic effector tissues do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Some of these are motor fibers that cause the release of ATP and possibly other purines related to it. Purine-evoked responses have been identified in the bronchi, gastrointestinal tract, and urinary tract. Other motor fibers are peptidergic, ie, they release peptides as the primary transmitters (see list above under Cotransmitters). 

---