Cyclosomatostatin

Stimulation of capsaicin-sensitive peripheral sensory nerve terminals induces remote anti-inflammatory effects throughout the body of anesthetized rats and guinea-pigs mediated by somatostatin. As somatostatin has also antinociceptive effects, the study aimed at investigating whether similar remote antinociceptive effects can be demonstrated in awake animals. In conscious rats, nociceptive nerve endings of the right hind paw decentralized by cutting the sciatic and saphenous nerves 18h before were chemically stimulated, and drop of the noxious heat threshold (heat hyperalgesia) induced by prior (18h before) plantar incision was measured on the contralateral, left hind paw using an increasing-temperature water bath. 18h after nerve transection, mustard oil-evoked plasma extravasation was not significantly reduced in the right hind paw as tested by in vivo fluorescence imaging. Applying agonist of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptor (capsaicin or mustard oil, respectively) to the nerve-transected paw inhibited the plantar incision-induced drop of the noxious heat threshold on the contralateral paw. The onset of these remote antihyperalgesic effects was 10-20min.

Enzymatic degradations of arginine-vasopressin (AVP) and its [7-sarcosine]-substituted analogs were performed using homogenates of rat kidney, liver and serum. Under the experimental conditions used in this work, [Sar7]AVP and the parent hormone were inactivated much faster by the kidney cortex and liver homogenates than the remaining analogs, which were additionally modified at position 1 and did not contain the N-terminal amino group. Analytical data of the degradation products showed that, in the case of AVP and [Sar7]AVP, there were two major sites of cleavage: Tyr-Phe and Arg-Gly. The analogs which lack free N-terminal amino groups were deactivated very slowly. In these cases the main degradation product resulted from the cleavage of the Arg-Gly bond. The most surprising result observed during the incubation of AVP and its analogs with rat serum was the relatively high enzymatic stability of the parent hormone compared with the modified analogs. In contrast, the fastest degradation rate was found for [Cpp1,Sar7]AVP, which contains the bulky cyclopentamethylene moiety in position 1. The cleavage of the Arg-Gly peptide bond was exclusively responsible for the inactivation of all peptides with rat serum.

This electrophysiological study examined whether octreotide, a stable analogue of somatostatin (SOM), reduces the mechanosensitivity of fine primary afferents from inflamed knee joints of rats similarly to SOM itself (Pain 73 (1997) 377). Close intra-arterial application of 200 microl of octreotide (10(-6)-10(-3) M) dose-dependently diminished the responses to passive non-noxious and noxious rotations of the joint in most of the units tested. The inhibitory effects of octreotide required a higher concentration (10(-3) M) compared to SOM to successfully decrease the number of recorded spikes. Application of cyclo-somatostatin, a SOM antagonist, before the octreotide injection prevented the reduction of the movement evoked discharges. These data indicate that octreotide is able to successfully decrease the responses of mechanosensitive fine afferent units innervating the inflamed knee joint of the rat and may, therefore, be useful in the treatment of articular pain of peripheral origin.