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. 1993 Apr;108(4):1150–1155. doi: 10.1111/j.1476-5381.1993.tb13519.x

Pharmacological characterization of the contractile responses to angiotensin analogues in guinea-pig isolated longitudinal muscle of small intestine.

A B Hawcock 1, J C Barnes 1
PMCID: PMC1908167  PMID: 8485624

Abstract

1. The contractile responses to angiotensin II, angiotensin III and two synthetic analogues, [Lys2]angiotensin II and [Sar1]angiotensin II, in the guinea-pig isolated longitudinal muscle preparation of small intestine have been characterized in vitro. 2. Tachyphylaxis to the angiotensin analogues was reduced by use of a Krebs-Henseleit solution containing a raised (sub-contractile) concentration of potassium (11.2 mM). Under these conditions. reproducible cumulative concentration-response curves to all agonists were established. The pD2 estimates for angiotensin II, [Lys2]angiotensin II, angiotensin III and [Sar1]angiotensin II were 9.15 +/- 0.14, 7.42 +/- 0.06, 7.69 +/- 0.18 and 9.50 +/- 0.15 respectively and the maximum responses achieved were not significantly different. 3. The contractile responses to angiotensin II, angiotensin III and [Sar1]angiotensin II were reduced by greater than 80% by tetrodotoxin (TTX; 0.1 microM). However, the responses to [Lys2]angiotensin II were reduced by only 63 +/- 5%. Atropine (0.1 microM) also reduced the responses to angiotensin II, angiotensin III and [Lys2]angiotensin II, although its effect was less than that produced by TTX. Furthermore, while responses to these agonists were not significantly modified by the NK1 receptor antagonist (+/-)-CP-96,345 (30 nM) alone, the combined pre-incubation with both atropine and (+/-)-CP-96,345 reduced maximum agonist responses to a level not significantly different from those produced by TTX. 4. Indirect and direct contractile responses to angiotensin II and [Lys2]angiotensin II (in the presence of TTX) respectively were characterized by use of the selective AT1 receptor antagonist, losartan and the AT2 receptor antagonist, PD123177.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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