Effect of a long-acting somatostatin analogue (octreotide) on circulating tachykinins and the pentagastrin-induced carcinoid flush
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Summary
Cutaneous flushing was provoked in seven patients with metastatic carcinoid tumours and the carcinoid syndrome by an intravenous injection of pentagastrin (0.6 µg·kg−1 body weight). The patients were studied before and 1 h after a subcutaneous injection of the long-acting somatostatin analogue octreotide 50 µg (Sandostatin). The severity of the carcinoid flush in all the patients was reduced by administration of the analogue. The rise in facial temperature was 1.3 (0.3)° C before and 0.8 (0.2)° C after octreotide.
Six patients responded to pentagastrin with a rise in the circulating neurokinin A-like immunoreactivity (NKA-LI) and five patients with a rise in circulating substance P-like immunoreactivity (SP-LI). No cutaneous flushing or rise in tachykinin concentration was observed in healthy subjects (n=6) after injection of pentagastrin. The rise in NKA-LI in the patients was decreased by 61 (14)% and the rise in SP-LI by 54 (13)% after octreotide. Although flushing still occurred, the tachykinin response in two patients was completely abolished.
The data demonstrate that the release of tachykinins from carcinoid tumours during pentagastrin-induced flushing is subject to partial inhibition by octreotide. However, the occurrence of a flush in some patients in the absence of a detectable rise in circulating tachykinins indicates that the latter peptides cannot be the sole causative agent of the carcinoid flush.
Key words
substance P neurokinin A neuropeptide K carcinoid syndrome somatostatin analogue octreotidePreview
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References
- 1.Creutzfeldt W, Stöckmann F (1987) Carcinoids and carcinoid syndrome. Am J Med 82 [Suppl 5B]: 4–16PubMedCrossRefGoogle Scholar
- 2.Frölich JC, Bloomgarden ZT, Oates JA, McGuigan JE, Rabinowitwz D (1978) The carcinoid flush. Provocation by pentagastrin and inhibition by somatostatin. N Engl J Med 299: 1055–1957PubMedCrossRefGoogle Scholar
- 3.Bauer W, Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher TJ, Pless J (1982) SMS 201-995: A very potent and selective octapeptide analogue of somatostatin with prolonge action. Life Sci 31: 1133–1141PubMedCrossRefGoogle Scholar
- 4.Kraenzlin ME, Ch'ng JC, Wood SM, Bloom SR (1983) Can inhibition of hormone secretion be associated with endocrine tumour shrinkage. Lancet 2: 1501PubMedCrossRefGoogle Scholar
- 5.Maton PN, O'Dorisio TM, Howe BA, McArthur KE, Howard JM, Cherner JA, Malarkey TB, Collen MJ, Gardner JD, Jensen RT (1985) Effect of a long-acting somatostatin analogue (SMS 201-995) in a patient with pancreatic cholera. N Engl J Med 312: 17–21PubMedCrossRefGoogle Scholar
- 6.Buchanan KD, Shaw C, O'Hare MMT, Dalzell G (1986) Evaluation of SMS 201-995 in gastrointestinal APUDomas. Scand J Gastroenterol 21 [Suppl 119]: 199–205Google Scholar
- 7.Wood SM, Kraenzlin ME, Adrian TE, Bloom SR (1985) Treatment of patients with pancreatic endocrine tumours using a new long-acting somatostatin analogue: Symptomatic and peptide responses. Gut 26: 438–444PubMedGoogle Scholar
- 8.Stöckmann F, Richter G, Lembcke B, Conlon JM, Creutzfeldt W (1986) Long-term treatment of patients with endocrine gastrointestinal tumours with the somatostatin analogue SMS 201-995. Scand J Gastroenterol 21 [Suppl 119]: 230–237Google Scholar
- 9.Schrezenmeir J, Plewe G, Stürmer W, Kahaly G, Oppermann D, Krause U, Del Pozo E, Kasper H, Beyer J (1986) Treatment of APUDomas with the long-acting somatostatin analogue SMS 201-995. Investigations of therapeutic use and digestive side-effects. Scand J Gastroenterol 21 [Suppl 119]: 223–227Google Scholar
- 10.Comi RJ, Gesundheit N, Murry L, Gordon P, Weintraub RD (1987) Response of thyrotropin-secreting pituitary adenomas to a long-acting somatostatin analogue. N Engl J Med 317: 12–17PubMedCrossRefGoogle Scholar
- 11.Von Werder K, Losa M, Müller OA, Schweiberer L, Fahlbusch R, Del Pozo E (1984) Treatment of metastasising GRF-producing tumour with a long-acting somatostatin analogue. Lancet 2: 282–283CrossRefGoogle Scholar
- 12.Kvols LK, Moertel CG, O'Connell MJ, Shutt AJ, Rubin J, Hahn RG (1986) Treatment of the malignant carcinoid syndrome. N Engl J Med 315: 663–666PubMedCrossRefGoogle Scholar
- 13.Richter G, Stöckmann F, Lembcke B, Conlon JM, Creutzfeldt W (1986) Short-term administration of the somatostatin analogue SMS 201-995 in patients with carcinoid tumours. Scand J Gastroenterol 21 [Suppl 119]: 193–198Google Scholar
- 14.Emson PC, Gilbert RFT, Martensson H, Nobin A (1984) Elevated concentrations of substance P and 5-HT in plasma in patients with carcinoid tumors. Cancer 54: 715–718PubMedCrossRefGoogle Scholar
- 15.Norheim I, Theodorsson-Norheim E, Brodin E, Öberg K (1986) Tachykinins in carcinoid tumors. Their use as tumor marker and possible role in the carcinoid flush. J Clin Endocrinol Metab 63: 605–612PubMedCrossRefGoogle Scholar
- 16.Conlon JM, Deacon CF, Richter G, Stöckmann F, Creutzfeldt W (1987) Circulating tachykinins (substance P, neurokinin A, neuropeptide K) and the carcinoid flush. Scand J Gastroenterol 22: 97–105PubMedGoogle Scholar
- 17.Falkmer S, Martensson H, Nobin A, Sundler F (1984) Peptide hormones in various types of gastro-entero-pancreatic tumors: immunohistochemical patterns and evolutionary background. Prog Cancer Res Ther 31: 597–610Google Scholar
- 18.Del Pozo E, Neufeld M, Schlüter K, Tortosa F, Clarenbach P, Bieder E, Wendel L, Nüesch E, Marbach P, Cramer H, Kerp L (1986) Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration. Acta Endocrinol 111: 433–439PubMedGoogle Scholar
- 19.Conlon JM, Sheehan L (1983) Conversion of substance P to C-terminal fragments in human plasma. Regul Pept 7: 335–345PubMedCrossRefGoogle Scholar
- 20.Deacon CF, Conlon JM (1987) Biosynthesis of tachykinins (substance P, neurokinin A and neuropeptide K) in neurons of the guinea pig myenteric plexus. Neurochem Int 10: 559–564CrossRefPubMedGoogle Scholar
- 21.Conlon JM, Deacon CF, Richter G, Schmidt WE, Stöckmann F, Creutzfeld W (1986) Measurement and partial characterization of the multiple forms of neurokinin A-like immunoreactivity in carcinoid tumours. Regul Pept 13: 183–186PubMedCrossRefGoogle Scholar
- 22.Kraenzlin ME, Wood SM, Neufeld M, Adrian TE, Bloom SR (1985) Effect of long acting somatostatin-analogue SMS 201-995 on gut hormone secretion in normal subjects. Experientia 41: 739–740CrossRefGoogle Scholar
- 23.Martling C-R, Theodorsson-Norheim E, Norheim I, Lundberg JM (1987) Bronchoconstrictor and hypotensive effects in relation to pharmacokinetics of tachykinins in the guinea pig — evidence for extraneuronal cleavage of neuropeptide K to neurokinin A. Naunyn Schmidebergs Arch Pharmacol 33: 183–189CrossRefGoogle Scholar
- 24.Schaffalitzky de Muckadell OB, Aggestrup S, Stentoft P (1986) Flushing and plasma substance P concentrations during infusions of synthetic substance P in normal man. Scand J Gastroenterol 21: 498–502PubMedGoogle Scholar
- 25.Balks HJ, Conlon JM, Creutzfeldt W, Stöckmann F (1988) Circulating bradykinin-like immunoreactivity and the pentagastrin-induced carcinoid flush. Clin Endocrinol 28: 141–151Google Scholar
- 26.Oates JA, Melmon K, Sjoerdsma A, Gillespie L, Mason DT (1964) Release of a kinin peptide in the carcinoid syndrome. Lancet 2: 514–517CrossRefGoogle Scholar