thioperamide and alpha-methylhistidine

A metamorphic life-history is present in the majority of animal phyla. This developmental mode is particularly prominent among marine invertebrates with a bentho-planktonic life cycle, where a pelagic larval form transforms into a benthic adult. Metamorphic competence (the stage at which a larva is capable to undergo the metamorphic transformation and settlement) is an important adaptation both ecologically and physiologically. The competence period maintains the larval state until suitable settlement sites are encountered, at which point the larvae settle in response to settlement cues. The mechanistic basis for metamorphosis (the morphogenetic transition from a larva to a juvenile including settlement), i.e. the molecular and cellular processes underlying metamorphosis in marine invertebrate species, is poorly understood. Histamine (HA), a neurotransmitter used for various physiological and developmental functions among animals, has a critical role in sea urchin fertilization and in the induction of metamorphosis. Here we test the premise that HA functions as a developmental modulator of metamorphic competence in the sea urchin Strongylocentrotus purpuratus.. Our results provide strong evidence that HA leads to the acquisition of metamorphic competence in S. purpuratus larvae. Pharmacological analysis of several HA receptor antagonists and an inhibitor of HA synthesis indicates a function of HA in metamorphic competence as well as programmed cell death (PCD) during arm retraction. Furthermore we identified an extensive network of histaminergic neurons in pre-metamorphic and metamorphically competent larvae. Analysis of this network throughout larval development indicates that the maturation of specific neuronal clusters correlates with the acquisition of metamorphic competence. Moreover, histamine receptor antagonist treatment leads to the induction of caspase mediated apoptosis in competent larvae.. We conclude that HA is a modulator of metamorphic competence in S. purpuratus development and hypothesize that HA may have played an important role in the evolution of settlement strategies in echinoids. Our findings provide novel insights into the evolution of HA signalling and its function in one of the most important and widespread life history transitions in the animal kingdom--metamorphosis.

Topics: Animals; Apoptosis; Chlorpheniramine; Cimetidine; Ectoderm; Gene Expression Regulation, Developmental; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Histamine H3 Antagonists; Histidine Decarboxylase; Larva; Metamorphosis, Biological; Methylhistidines; Organ Specificity; Piperidines; Receptors, Histamine H1; Strongylocentrotus purpuratus

We assessed the functional role of the histamine H3-receptor in conscious intact rats during activation of the sympathoadrenal axis.. Male Sprague-Dawley rats, with or without cerebroventricular cannula, were subjected to mild footshocks and mean arterial pressure (MAP) and heart rate were determined using a tail-cuff plethysmograph.. Saline, phentolamine (3 mg/kg, i.p.), (R)-alphafluoromethylhistidine (AFMH) (100 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), (R)-alphamethylhistamine (AMH) (2 mg/kg, i.p. or 100 microg/5 microl, i.v.t.), thioperamide (THIO) (1 or 2 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), mepyramine (10 mg/kg, i.p.), cimetidine (2 mg/kg, i.p.).. Urinary catecholamines were determined by fluorometry. Statistical differences between experimental groups were evaluated by Student's t-test or one-way ANOVA.. Footshocks increased both MAP and heart rate. The vasopressor response to footshocks was facilitated (p < 0.001) by i.p. administration of AFMH, a histidine decarboxylase inhibitor, or THIO, a H3-receptor antagonist, but not by i.v.t. injection of these drugs. AMH, a H3-receptor agonist, given i.p., decreased the vasopressor response to footshocks (p < 0.001). This action of AMH was abolished by THIO but not by mepyramine or cimetidine. The MAP response to exogenous norepinephrine was not altered by i.p. administration of either AFMH or THIO.. Our results demonstrate an involvement of peripheral histamine H3 prejunctional receptors in the inhibitory modulation of peripheral noradrenergic responses during stress.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cimetidine; Electric Stimulation; Enzyme Inhibitors; Heart Rate; Hindlimb; Histamine Antagonists; Histamine H1 Antagonists; Histamine H2 Antagonists; Male; Methylhistidines; Norepinephrine; Phentolamine; Piperidines; Pyrilamine; Rats; Rats, Sprague-Dawley; Receptors, Histamine H3; Vasoconstrictor Agents