Anti‐inflammatory effect of synthetic somatostatin analogues in the rat

• Published in: British journal of pharmacology Vol. 134; no. 7; pp. 1571 - 1579
• Main Authors: Helyes, Zsuzsanna, Pintér, Erika, Németh, József, Kéri, György, Thán, Márta, Oroszi, Gábor, Horváth, Anikó, Szolcsányi, János
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2001; Nature Publishing
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; anti‐inflammatory effect; Arthritis, Experimental - pathology; Arthritis, Experimental - prevention & control; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Bradykinin - administration & dosage; Capillary Permeability - drug effects; Dextrans - administration & dosage; dextran‐oedema; diclofenac; Diclofenac - pharmacology; Dose-Response Relationship, Drug; Evans Blue - metabolism; Female; Freund adjuvant; Hindlimb - drug effects; Hindlimb - innervation; Hindlimb - pathology; In Vitro Techniques; Inflammation - chemically induced; Inflammation - prevention & control; Injections, Intraperitoneal; Medical sciences; meloxicam; mustard oil; Neurogenic inflammation; neuropeptide release; Neuropeptides - drug effects; Neuropeptides - secretion; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; somatostatin analogues; Thiazines - pharmacology; Thiazoles - pharmacology; Time Factors; Trachea - drug effects; Trachea - metabolism; Treatment Outcome; TT‐232; Prostaglandin-endoperoxide synthase; Intraperitoneal administration; Intravenous administration; Rat; Diseases of the osteoarticular system; Arthritis; Neuropeptide; Blood; Blood plasma; Extravasation; Subcutaneous administration; Neurogenic inflammation; Somatostatin; Immune system; Immune response; Enzyme; Rodentia; Antiinflammatory agent; Enzyme inhibitor; Inflammation; Joint; In vitro; Long term; Biological activity; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Arthropathy; Oxidoreductases
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704396

Somatostatin (6.11 nmol kg−1 i.p.) inhibited neurogenic plasma extravasation evoked by 1% mustard oil and non‐neurogenic oedema induced by 5% dextran in the rat skin.
Cyclic synthetic octapeptide (TT‐248 and TT‐250) and heptapeptide (TT‐232) somatostatin analogues proved to be more effective in reducing neurogenic and non‐neurogenic inflammatory reactions but octreotide had no influence on either neurogenic or non‐neurogenic inflammation.
TT‐232 administered i.p. or i.v. (1.06 – 42.40 nmol kg−1) inhibited in a dose‐dependent manner the plasma extravasation evoked by mustard oil in the rat's paw. Neither diclofenac (15.78 – 315.60 μmol kg−1) nor the selective COX‐2 inhibitor meloxicam (2.95 – 569.38 μmol kg−1) attenuated the mustard oil‐induced neurogenic plasma extravasation.
TT‐232, diclofenac and meloxicam dose‐dependently diminished non‐neurogenic dextran‐oedema of the paw the ED35 values were 1.73 nmol kg−1 for TT‐232 and 34.37 μmol kg−1 for diclofenac.
TT‐232 inhibited in the dose range of 1.06 – 21.21 nmol kg−1 the bradykinin‐induced plasma extravasation in the skin of the chronically denervated paw.
Mustard oil‐induced cutaneous plasma extravasation was dose‐dependently diminished by s.c. TT‐232 1, 2, 4, 6 or 16 h after the treatment. TT‐232 (2×106, 2×212 and 2×530 nmol kg−1 per day s.c. for 18 days) caused dose‐dependent inhibition of chronic Freund adjuvant‐induced arthritis during the experimental period.
TT‐232 (200 and 500 nM) inhibited the release of SP, CGRP and somatostatin from the rat isolated trachea induced by electrical field stimulation (40 V, 0.1 ms, 10 Hz, 120 s) or by capsaicin (10−7 M), but did not influence the basal, non‐stimulated peptide release.
It is concluded that somatostatin analogues without endocrine functions as TT‐232 are promising compounds with a novel site of action for inhibition of non‐neurogenic and neurogenic inflammatory processes.
British Journal of Pharmacology (2001) 134, 1571–1579; doi:10.1038/sj.bjp.0704396