Dual effects of α₂‐adrenoceptors in modulating myogenic tone in sheep isolated internal anal sphincter

Abstract

We conclude that α2 -adrenoceptors can mediate contraction of IAS, although this effect is most evident with efficacious imidazoline agonists rather than the most selective ligand. In addition, this receptor subtype can directly inhibit noradrenergic contractile responses to EFS and, indirectly, enhance nitrergic relaxatory responses.

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

“…In agreement with a previous report, high-dose dexmedetomidine-induced contraction was attenuated by prazosin at a concentration of 3 x 10 -9 M, which corresponds to the concentration of prazosin necessary to inhibit alpha-1 adrenoceptors 16 , 19 . Dexmedetomidine shows a low affinity for the alpha-1 adrenoceptor and is a partial agonist of the human alpha-1B adrenoceptor 9 , 10 . Taking previous findings into consideration, the putative mechanism associated with the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction is as follows 9 , 10 .…”

“…Dexmedetomidine shows a low affinity for the alpha-1 adrenoceptor and is a partial agonist of the human alpha-1B adrenoceptor 9 , 10 . Taking previous findings into consideration, the putative mechanism associated with the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction is as follows 9 , 10 . Although dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist (α 2 /α 1 selectivity ratio: 1620) compared with other alpha-2 adrenoceptor agonists, at high doses, dexmedetomidine may occupy a small proportion of alpha-1 adrenoceptors 2 .…”

“…Furthermore, dexmedetomidine attenuates the contraction induced by the alpha-1 adrenoceptor agonist phenylephrine in isolated vessels 7 , 8 . In addition, it has been reported that dexmedetomidine shows low affinity for the alpha-1 adrenoceptor 9 , 10 . These previous reports suggest that high doses of dexmedetomidine induce competitive inhibition at the alpha-1 adrenoceptor via the intrinsic low affinity of dexmedetomidine for the alpha-1 adrenoceptor 7 - 10 .…”

The Effect of Dexmedetomidine Sedation on Lower Gastrointestinal Motility in Children—Is It Suitable for Anorectal Manometry?

“…The internal anal sphincter is derived from the circular muscle layer of the rectum, and is composed primarily of smooth muscle. Previous studies have shown that the internal anal sphincter contributes to the majority of the resting IASP (75-85%) [14], and, therefore, it is expected that general anesthesia will influence the anal sphincter function and its relaxation [15].…”

“…However, the effects on the lower gastrointestinal tract in humans suggest that DEX may have a positive effect on improving return of motility following abdominal surgery in adult patients [27]. Results of animal experiments have suggested that α-adrenoceptor mediated pathways may play a role in modulating smooth muscle motility, but mixed effects have been reported [15,17,25,28,29].…”