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. 1995 Jan;114(1):49–56. doi: 10.1111/j.1476-5381.1995.tb14904.x

Characterization of the interaction between muscarinic M2 receptors and beta-adrenoceptor subtypes in guinea-pig isolated ileum.

H Reddy 1, N Watson 1, A P Ford 1, R M Eglen 1
PMCID: PMC1510155  PMID: 7712028

Abstract

1. Contraction of guinea-pig ileum to muscarinic agonists is mediated by M3 receptors, even though they account for only 30% of the total muscarinic receptor population. The aim of this study was to characterize the biochemical and functional effects of stimulation of the predominant M2 muscarinic receptor (70%) and to investigate the hypothesis that M2 receptors specifically oppose beta-adrenoceptor-mediated effects in the ileum. 2. In guinea-pig ileal longitudinal smooth muscle slices, isoprenaline, a non-selective beta-adrenoceptor agonist, and BRL 37344 (sodium-4-[2-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl]-phenoxyacetate sesquihydrate), a beta 3-adrenoceptor selective agonist, increased cyclic AMP accumulation with -log EC50 values of 6.6 +/- 0.1 and 5.8 +/- 0.1 respectively. Maximal stimulation by BRL 37344 (10 microM) was 26.4 +/- 5.2% of that observed with isoprenaline (10 microM). Isoprenaline (10 microM)-stimulated cyclic AMP accumulation was significantly, but not completely, inhibited by propranolol (5 microM), with a propranolol-resistant component of 28.2 +/- 6.8% of the maximal stimulation to isoprenaline. In contrast, basal and BRL 37344 responses were resistant to this antagonist. These data provide evidence that both beta 1- and beta 3-adrenoceptors activate adenylyl cyclase in guinea-pig ileum. 3. Isoprenaline (10 microM)-stimulated cyclic AMP accumulation was inhibited (67.4 +/- 0.9%) by the muscarinic agonist (+)-cis-dioxolane (-log EC50 = 7.3 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

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