Pharmacological examinations of isolated auricles from Sepia officinalis were carried out to analyze the putative role of the monoaminergic transmitter/receptor system in the control of auricle function. In conjunction with histofluorescence studies and HPLC analyses, evidence of a double excitatory serotonergic and noradrenergic innervation of the auricles was obtained. Serotonin-induced positive chronotropic and inotropic effects were blocked by mianserin (5-HT1 and 5-HT2) but not by cyproheptadine (5-HT2). It is assumed that the auricular serotonin (5-HT) receptor represents a 5-HT1-like subtype and is not identical to the ventricular 5-HT receptor. Noradrenaline, adrenaline and dopamine evoked mainly positive chronotropic reactions and less prominent positive inotropic reactions. The potency range (pD2 frequency: noradrenaline 6.65 >> adrenaline 5.69 > dopamine 5.34; pD2 amplitude: noradrenaline 6.09 (greater than or equal to) adrenaline 5.91 > dopamine 5.33) indicates out that noradrenaline might be the effective neurotransmitter in vivo. The α -mimetics clonidine (α 2) and phenylephrine (α 1) induced positive chronotropic and inotropic effects, while the β-mimetics albuterol (β2>β1) and dobutamine (β1) revealed only positive inotropic reactions. The β-agonist isoprenaline mimicked the positive chronotropic effects of noradrenaline and induced the strongest positive inotropic effects of all the agonists tested. Urapidil (α 1) or phentolamine (α 1 and α 2) blocked only the positive chronotropic effects of noradrenaline and isoprenaline. The positive inotropic effects of isoprenaline could be blocked by the adenylate cyclase inhibitors MDL-12,330A or SQ-22, 536, which had no effect on the chronotropic effects of isoprenaline. These results suggest that two catecholaminergic receptors are present in the auricles of Sepia officinalis: an α -like adrenoreceptor mediating mainly chronotropic effects, and a β-like receptor which appears to mediate inotropic effects by activating the cyclic AMP pathway. These results suggest that the auricles exert a regulatory effect on ventricular performance.
