A pharmacological investigation of histamine H1- and H2- receptors in the brain of the pulmonate mollusc, Helix aspersa

Pharmacological experiments were carried out to determine whether both H1 and H types of histamine (Hm) receptor were present in the brain of the snail, fiolix asversa, as had been demonstrated in vertebrates. The nature and specificity of the receptors were examined using three antagonists and five agonists of Hm. General studies were performed on identified neurones in the suboesophageal ganglia. Hm was applied to the bath and also by iontophoresis. Fifty-five cells gave responses to Hm and both depolarization (D) and by perpolarization (H) responses were observed. A few responses were biphasic. Seventeen cells were antagonized by mepyramine (H); both D and H, responses were blocked. Three cells were partially antagonized by metiamide (H 2).The agonists 2-metbylhistamine (H ) and 4-methylhistamine (H ) were compared with Hm on thirteen cells. Neither agonist was more potent than Hm (E.P.M. & . >1), 2-metbylhistamine being more potent than 4-methylhistamine for the majority of cells tested. Intensive studies were performed on two D and two H cells to Hm, which responded strongly to iontophoretic Hm. Agonist and antagonist experiments indicated. that E2, E13 and E14 possessed H - receptors, while F3a possessed both H - and H2 receptors. These results were used to assess the possibility that HM might have a neurotransmitter function in the snail brain. Experiments were carried out on a cell, identified as E3, to verify that the left pallial nerve (LPN) produced long-lasting depression of the anal nerve (AN) epsp by a presynaptic mechanism. This was not found to be so, for after a short stimulation of the LPN, the inhibition of the AN epsp was only obtained over a short time-course of approximately 10 seconds. This paralleled the inhibition produced by repetitive stimulation of the AN. A similar short-term inhibition of the LL N epsp was noted-after prior stimulation of the AN, indicating that the effect was non-specific. Comparable effects were also obtained on several other cells and various nerve pairs were used as conditioning and test pathways. The effects were mostly short-term depressions, but one or two instances of facilitation were observed. Possible mechanisms for these short-term heterosynaptic interactions were described.