The effect of histamine on field-stimulated contractions of the guinea-pig prostate.
The aim of this study was to investigate the effect of histamine on field-stimulated contractions of the guinea-pig prostate using isolated preparations in organ bath experiments. The histamine receptor subtype involved in potentiating the twitch responses was characterised, and the presence of any post-synaptic effects was determined. In addition, the effects of histamine on nerve-stimulated contractions of the ventral and dorsal prostate as well as the coagulating gland were compared in preliminary experiments. Histamine (300 microM) approximately doubled the magnitude of the twitch contractions in the ventral and dorsal lobes of the prostate (nerve stimulation parameters were 10 Hz for 2 s every 50 s, 0.5 ms duration at supramaximal voltage). In the coagulating glands, histamine increased the contractions more than fourfold. Further experiments were performed only on the ventral glands. The H(1) receptor antagonist, mepyramine, exhibited an apparent competitive antagonism against the histamine-induced potentiations of the twitch responses (apparent pK(B) value = 9.21+/-0.17 (n=5). The H(2) receptor antagonist, ranitidine, produced a small, significant shift to the right, as did the time control. The H(3) receptor antagonist, thioperamide, had no significant effect on the concentration-response curve. The effects of histamine (10 microM) on exogenously applied acetylcholine (Ach), noradrenaline (NA) and adenosine 5'-triphosphate (ATP) were determined. In each case, the contractile responses were significantly potentiated: ATP (5.8-fold P<0.0001, n=8), NA (1.6-fold P<0.05, n=10) and Ach (2.1-fold P<0.0007, n=10). This is the first study that has shown the effects of histamine on field-stimulated contractions in the prostate of any species. It is concluded that histamine, acting on H(1) receptors, elicits a considerable potentiation of the nerve-stimulated twitch contractions in the guinea-pig prostate. One mechanism whereby histamine exerts its potentiating effect is a post-synaptic enhancement of the response to ATP in particular, but also to NA and Ach. It is suggested that H(1)-receptor and purinoceptor antagonists may have a role to play in the treatment of benign prostatic hyperplasia (BPH).
Kerr
Karen P
KP
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia. Karen.Kerr@vcp.monash.edu.au
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism
D006632:Histamine; D000255:Adenosine Triphosphate