Characterization of the Rabbit Detrusor Response to Histamine through Pharmacologic Antagonism

Abstract

The various effects of histamine on smooth muscles and other tissues are thought to be mediated by two pharmacologically distinct receptors, H_t and H₂ types. These receptors are defined in terms of their susceptibility to blockade by pyrilamine (typeíi!) or burimamide (typeH₂). In this study selective antagonism of the spasmodic effects of histamine on isolated strips of rabbit detrusor has shown that the response is mediated by H₁ receptors, with no evidence of H₂ activity. The p^A2 of the pyrilamine-histamine antagonism is 9.3. The histamine response is susceptible to muscarinic blockade (atropine and propantheline) but not to nicotinic blockade (hexamethonium). Adrenergic blocking agents propranolol (10^–4M) and phenoxybenzamine (10^–8M) do antagonize the contractile response, but this does not appear to be indicative of adrenergic mediation.

In vitro characterization of .ALPHA.-adrenergic receptor in rabbit detrusor muscle.

“…By comparing the responses caused by selected agonists and antagonists, the present study confirmed that H, -histaminergic re ceptors (3,9,10) and M2-muscarinic receptors (11, 23) mediated contraction of the detrusor muscle of the urinary bladder. rabbit trigone, urethra and prostate, which has been shown in our previous study (17) where ai -adrenergic receptors were demon strated to mediate contraction.…”

“…H1-histami nergic receptors (3,9,10) and M2-muscarinic receptors (11) have been reported to mediate contraction of the detrusor muscle; however, a-adrenergic receptor subtype to mediate the contraction of the detrusor muscle still remains unknown.…”

Comparison of the Urinary Bladder Base and Detrusor to Cholinergic and Histaminergic Receptor Activation in the Rabbit

“…Re sponses for cholinergic, /32-adrenergic (2,9), and H] histaminergic (10) ceptors reported by Edvardsen and Setekleiv (8) and Sigg and Sigg (14). Recently, however, interest in the bladder base and neck regions has increased and several studies have now been reported in the rabbit bladder by Van Buren and Anderson (17), Downie et al (7) and in the human and guinea pig by Khanna et al (12).…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…The effects of the amine on isolated urinary tract smooth muscle have been studied by several investigators. In the rabbit and guinea pig urinary bladder, histamine was suggested to produce contraction through H 1 -receptors located on the smooth muscle (Fredericks, 1975;Khanna et al, 1977;Kondo et al, 1985;Poli et al, 1988). However, in the rabbit bladder, part of the contraction seemed to be mediated by release of acetylcholine, since the histamine-induced contraction was effectively inhibited by atropine or propantheline (Fredericks, 1975).…”

“…In the rabbit and guinea pig urinary bladder, histamine was suggested to produce contraction through H 1 -receptors located on the smooth muscle (Fredericks, 1975;Khanna et al, 1977;Kondo et al, 1985;Poli et al, 1988). However, in the rabbit bladder, part of the contraction seemed to be mediated by release of acetylcholine, since the histamine-induced contraction was effectively inhibited by atropine or propantheline (Fredericks, 1975). Poli et al (1988) found that histamine enhanced the atropine-resistant response to field stimulation and also suggested that H 1 receptors were involved in both types of response, but that the receptors populations pre-and postjunctionally were heterogeneous.…”