Characterization of the alpha1-adrenoceptor subtype mediating contractions of the pig internal anal sphincter.
OBJECTIVE
The internal anal sphincter has been shown to contract in response to alpha1-adrenoceptor stimulation and therefore alpha1-adrenoceptor agonists may be useful in treating faecal incontinence. This study characterizes the alpha1-adrenoceptor subtype responsible for mediating contraction of the internal anal sphincter of the pig.


METHODS
The potency of agonists and the affinities of several receptor subtype selective antagonists were determined on smooth muscle strips for the pig internal anal sphincter. Cumulative concentration-response curves were performed using phenylephrine and noradrenaline.


RESULTS
The potency of the alpha1A-adrenoceptor selective agonist A61603 (pEC50=7.79+/-0.04) was 158-fold greater than that for noradrenaline (pEC50=5.59+/-0.02). Phenylephrine (pEC50=5.99+/-0.05) was 2.5-fold more potent than noradrenaline. The alpha1D-adrenoceptor selective antagonist BMY7378 caused rightward shifts of the concentration-response curves to phenylephrine and noradrenaline, yielding low affinity estimates of 6.59+/-0.15 and 6.33+/-0.13, respectively. Relatively high affinity estimates were obtained for the alpha1A-adrenoceptor selective antagonists, RS100329 (9.01+/-0.14 and 9.06+/-0.22 with phenylephrine and noradrenaline, respectively) and 5-methylurapidil (8.51+/-0.10 and 8.31+/-0.10, respectively). Prazosin antagonized responses of the sphincter to phenylephrine and noradrenaline, yielding mean affinity estimates of 8.58+/-0.10 and 8.15+/-0.08, respectively. The Schild slope for prazosin with phenylephrine was equal to unity (1.01+/-0.24), however the Schild slope using noradrenaline was significantly less than unity (0.50+/-0.11, P<0.05).


CONCLUSIONS
The results suggest that contraction of circular smooth muscle from the pig internal anal sphincter is mediated via a population of adrenoceptors with the pharmacological characteristics of the alpha1A/L-adrenoceptor, most probably the alpha1L-adrenoceptor form of this receptor.
Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia.
Ka
K
Mills
N
N
Hausman
R
R
Chess-Williams
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D001003:Anal Canal / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1