Does serotonin relax the rat anococcygeus muscle via 5-HT 7 receptors?

Abstract

The mechanisms of serotonin (5-HT)-induced contraction and relaxation were studied in the rat anococcygeus muscle. In the presence of prazosin (1 nM) and ketanserin (10 nM), concentration/response curves to 5-HT were shifted to the right and the maximum effects were not affected (pKB values 9.09+/-0.29 and 8.66+/-0.06 for prazosin and ketanserin, respectively). On contrary, guanethidine (10 microM) antagonised the 5-HT-induced contractions non-competitively. In the presence of guanethidine, prazosin or ketanserin further inhibited the responses to 5-HT at lower concentrations. The serotonergic receptor agonists 5-carboxamidotrypamine, metoclopramide and sumatriptan did not produce any effect in tissues under baseline conditions. 5-HT caused concentration-dependent relaxation in phenylephrine (1 microM) -precontracted preparations in the presence of guanethidine (10 microM). Tetrodotoxin (1 microM), N(G)-nitro-L-arginine (100 microM) and capsaicin (1 microM) were ineffective in antagonising the relaxation induced by 5-HT. The serotonergic receptor antagonists: ketanserin (0.1 microM), ICS 205930 (10 microM), GR 113808 (10 microM), GR 55562 (10 microM), methiothepin (10 nM), mesulergine (10 microM), ritanserin (0.1 microM) and spiperon (0.1 microM) did not antagonise 5-HT-induced relaxation. On the other hand, clozapine (0.01-0.1 microM) and metergoline (0.1-1 microM) attenuated the relaxation induced by 5-HT. These results demonstrate that 5-HT contracts rat anococcygeus muscle directly by an action on alpha1-adrenergic receptors and indirectly by releasing noradrenaline from adrenergic nerve endings. None of the 5-HT receptors plays a role in the 5-HT-induced contractions. Moreover 5-HT induces concentration-dependent relaxation in the precontracted preparations which apparently are not mediated through known 5-HT receptor types.

Calcium-Antagonistic Activity of Sumatriptan in the Rat Anococcygeus Muscle

“…Furthermore, the expression of 5-HT 7 receptor mRNA could not be observed in the rat anococcygeus muscle, excluding a role of 5-HT 7 receptors in these relaxations. These findings also give an answer to our previous question on 5-HT 7 receptors in the rat anococcygeus muscle [12]. The answer is that the rat anococcygeus muscle does not contain 5-HT 7 receptors, and, therefore, 5-HT 7 receptors do not play any role in the effects of sumatriptan and 5-HT [12] in this smooth muscle.…”

“…These findings also give an answer to our previous question on 5-HT 7 receptors in the rat anococcygeus muscle [12]. The answer is that the rat anococcygeus muscle does not contain 5-HT 7 receptors, and, therefore, 5-HT 7 receptors do not play any role in the effects of sumatriptan and 5-HT [12] in this smooth muscle. Most studies performed with mammalian cells expressing either recombinant 5-HT 1B or 5-HT 1D receptors have shown that these receptors are negatively coupled to adenylate cyclase [23,24].…”

“…In our previous study [12], we have shown for the first time that 5-HT relaxes the phenylephrine (PE)-precontracted rat anococcygeus muscle in a concentrationdependent manner. As a continuity, in the present study, we aimed at observing the effect of sumatriptan on the precontracted rat anococcygeus muscle and to define the mechanism of its effect.…”

5‐Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine, which is converted into nitric oxide

“…Moreover, 5‐HT counteracts smooth muscle contraction by stimulating sodium influx and hyperpolarizing the membrane, an effect mediated by 5‐HT2A ( Rhoden et al , 2000 ). On the other hand, several reports have shown that 5‐HT triggers the relaxation of smooth muscle cells by mechanisms independent of 5‐HT receptors, such as the relaxation induced in isolated guinea‐pig gallbladder strips and in the rat anococcygeus muscle ( Emre et al , 2000 ; Emre‐Aydingoz et al , 2001 ). The present results add another mechanism to explain the receptor‐independent smooth muscle relaxation elicited by 5‐HT.…”

Craniomandibular muscles, intraoral orthoses and migraine

“…Sumatriptan was developed as a cerebral vasoconstrictor, but it has also been shown to act on skeletal muscle [91][92][93]. It cannot be excluded, therefore, that the triptans may be effective in migraine due to altered muscle metabolism.…”