P.1.c.005 Polymorphism of the serotonin transporter promoter may predict the response to selective serotonin reuptake inhibitors in bulimia nervosa

Abstract

Conventional intracellular microelectrodes and marker injection techniques were used to study the actions of histamine on inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. Bath application of histamine (1–300 μM) reversibly suppressed both noradrenergic and non-adrenergic slow inhibitory postsynaptic potentials in a concentration-dependent manner. These effects of histamine were mimicked by the selective histamine H3 receptor agonist R(−)-α-methylhistamine but not the selective histamine H1 receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective histamine H2 receptor agonist, dimaprit. The histamine H3 receptor antagonist, thioperamide, blocked the effects of histamine. Histamine H1 and H2 receptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressure ejection from micropipettes were unaffected by histamine and R(−)-α-methylhistamine. The results suggest that histamine acts at presynaptic histamine H3 receptors on the terminals of sympathetic postganglionic fibers and intrinsic somatostatinergic nerves in the small intestine to suppress the release of the inhibitory neurotransmitters, norepinephrine and somatostatin.