Histamine H3-receptor signaling in the heart: Possible involvement of G(i)/G(o) proteins and N-type Ca++ channels Academic Article uri icon

Overview

MeSH Major

  • Adrenergic Fibers
  • Calcium Channels
  • GTP-Binding Proteins
  • Heart
  • Peptides
  • Pertussis Toxin
  • Receptors, Histamine H3
  • Signal Transduction
  • Virulence Factors, Bordetella

abstract

  • Discovered as inhibitory autoreceptors in central histaminergic pathways, histamine H3-receptors may also modulate peripheral cholinergic and central adrenergic function. Recently, H3-receptors were reported to inhibit adrenergic inotropic responses in guinea pig atria, possibly at prejunctional sites. We have assessed whether the H3-mediated modulation of cardiac adrenergic activities results from a reduction in norepinephrine release. We have found that (R) alpha-methylhistamine, the selective histamine H3-receptor agonist, attenuates the inotropic and chronotropic response of isolated guinea pig atria to transmural stimulation of adrenergic nerve endings. This attenuation was associated with a marked reduction in endogenous norepinephrine release. In contrast (R) alpha-methylhistamine did not modify the chronotropic effect of exogenous norepinephrine. The attenuation of adrenergic responses by (R) alpha-methylhistamine was 1) prevented by thioperamide, the selective H3-receptor antagonist; 2) attenuated by pertussis-toxin pretreatment and 3) potentiated by the N-type Ca(++)-channel blocker omega-conotoxin, which also potentiated the sympathetic modulatory effects of adrenergic-alpha 2 and adenosine-A1 receptor agonists. Our findings indicate that prejunctional histamine H3-receptors modulate the depolarization-dependent norepinephrine release from sympathetic nerve endings in the guinea pig myocardium. These receptors are probably coupled to a pertussis-toxin-sensitive Gi/Go protein and probably effect a reduction in Ca++ current. We have previously reported that sympathetic stimulation elicits a frequency-dependent release of cardiac histamine, whereas others had found that adrenergic activity regulates histamine's rapid turnover pool. Accordingly, presynaptic H3-receptors are likely to serve a modulatory role in cardiac adrenergic function.

publication date

  • May 17, 1994

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 8169830

Additional Document Info

start page

  • 221

end page

  • 9

volume

  • 269

number

  • 1