Abstract
Histamine is an important modulatory agent of the sympathetic neurotransmission, but its exact action on the testicular capsule or rat vas deferens is not fully understood. The present study sought to further investigate the functional effects of histamine on the neuronal and exogenous noradrenaline-induced contraction of the testicular capsule and rat vas deferens as well as to evaluate the contractile properties of this drug. The testicular capsule or vas deferens from Wistar rats, 3–4 months old, weighing 300–400 g, was isolated and mounted in organ baths for functional experiments. The results indicated that the neuronally evoked contraction of the testicular capsule was affected by histamine (10−10 to 10−8 M) with participation of inhibitory (H3 receptors) and excitatory (H1 receptors) receptors. Histamine (10−7 to 10−4 M) modulated the field-stimulated vas deferens by excitatory (H2 receptors) and inhibitory (H1 receptors) receptors. Histamine was able to decrease the tonic response for noradrenaline-induced contractions with participation of H1 receptors (testicular capsule) and H3 receptors (vas deferens) followed by nitric oxide generation. At high concentration, histamine exerts contractile effects in both tissues. In the testicular capsule, the histamine-induced contractions were related to H1 receptor activation followed by release of prostaglandins. In contrast, the contractile effects of histamine in the vas deferens were related to H2 receptor activation followed by release of catecholamines from sympathetic nerve endings. Therefore, our results indicate that histamine induced several effects on the sympathetic neurotransmission of rat testicular capsule and vas deferens. These effects are dependent on the concentration used and with participation of multiple histamine receptors.
Similar content being viewed by others
References
Albrecht M, Frungieri MB, Gonzalez-Calvar S, Meineke V, Kohn FM, Mayerhofer A (2005) Evidence for a histaminergic system in the human testis. Fertil Steril 83(4):1060–1063. doi:10.1016/j.fertnstert.2004.12.002
Banks FC, Knight GE, Calvert RC, Turmaine M, Thompson CS, Mikhailidis DP, Morgan RJ, Burnstock G (2006) Smooth muscle and purinergic contraction of the human, rabbit, rat, and mouse testicular capsule. Biol Reprod 74(3):473–480. doi:10.1095/biolreprod.105.044602
Bell C, McLean JR (1973) The autonomic innervation of the rat testicular capsule. J Reprod Fertil 32(2):253–258
Besse JC, Furchgott RF (1976) Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. J Pharmacol Exp Ther 197(1):66–78
Beukers MW, Klaassen CH, De Grip WJ, Verzijl D, Timmerman H, Leurs R (1997) Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells. Br J Pharmacol 122(5):867–874. doi:10.1038/sj.bjp.0701466
Bhalla P, Marshall I (1980) Histamine H2-receptor antagonists in the mouse isolated vas deferens [proceedings]. Br J Pharmacol 68(1):149P–150P
Campos MB, Vitale ML, Ritta MN, Chiocchio SR, Calandra RS (1990) Catecholamine distribution in adult rat testis. Andrologia 22(3):247–250
Caricati-Neto A, D’Angelo LC, Reuter H, Hyppolito Jurkiewicz N, Garcia AG, Jurkiewicz A (2004) Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens. Eur J Pharmacol 503(1–3):191–201. doi:10.1016/j.ejphar.2004.09.034
Chiavegatto S, Bernardi MM, de-Souza-Spinosa H (1989) Effects of prenatal diphenhydramine administration on sexual behavior in rats. Braz J Med Biol Res 22(6):729–732
de Almeida Kiguti LR, Pupo AS (2012) Investigation of the effects of alpha1-adrenoceptor antagonism and L-type calcium channel blockade on ejaculation and vas deferens and seminal vesicle contractility in vitro. J Sex Med 9(1):159–168. doi:10.1111/j.1743-6109.2011.02410.x
Djuric DM, Nesic MT, Andjelkovic IZ (1996) Endothelium-dependent relaxation of rat aorta to a histamine H(3) agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na, K-ATPase. Mediat Inflamm 5(1):69–74. doi:10.1155/S0962935196000129
Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000) The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52(4):595–638
Haidl G, Duan YG, Chen SJ, Kohn FM, Schuppe HC, Allam JP (2011) The role of mast cells in male infertility. Expert Rev Clin Immunol 7(5):627–634. doi:10.1586/eci.11.57
He G, Hu J, Ma X, Li M, Wang H, Meng J, Jia M, Luo X (2008) Sympathetic histamine exerts different pre- and post-synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens. J Neurochem 106(4):1710–1719. doi:10.1111/j.1471-4159.2008.05532.x
He G, Ma X, Lu J, Meng J, Chen Y, Jia M, Luo X (2009) Alpha2 adrenoceptors modulate histamine release from sympathetic nerves in the guinea pig vas deferens. Neuropharmacology 57(5–6):506–510. doi:10.1016/j.neuropharm.2009.07.029
Hew RW, Hodgkinson CR, Hill SJ (1990) Characterization of histamine H3-receptors in guinea-pig ileum with H3-selective ligands. Br J Pharmacol 101(3):621–624
Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL (1997) International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 49(3):253–278
Hu J, Chen T, Li M, He G, Meng J, Ma X, Wu Y, Jia M, Luo X (2007) Wide distribution and subcellular localization of histamine in sympathetic nervous systems of different species. Neurosci Res 59(2):231–236. doi:10.1016/j.neures.2007.06.1481
Jurkiewicz A, Jurkiewicz NH (1976) Dual effect of alpha-adrenoceptor antagonists in rat isolated vas deferens. Br J Pharmacol 56(2):169–178
Jurkiewicz NH, Jurkiewicz A, Gomes CB, Aucelio JG (1977) Pharmacodynamic analysis of the rat isolated vas deferens after transplantation to intestinal wall. J Pharmacol Exp Ther 203(1):112–119
Jurkiewicz NH, Caricati-Neto A, Verde LF, Avellar MC, Reuter HR, Jurkiewicz A (2006) Sympathetic neurotransmission in the rat testicular capsule: functional characterization and identification of mRNA encoding alpha1-adrenoceptor subtypes. Eur J Pharmacol 543(1–3):141–150. doi:10.1016/j.ejphar.2006.05.045
Langer SZ, Arbilla S (1990) Presynaptic receptors on peripheral noradrenergic neurons. Ann N Y Acad Sci 604:7–16
Liao CS, Day AR, Freer RJ (1981) Inhibitory histamine receptors in the rat vas deferens. Res Commun Chem Pathol 31(1):173–176
Ligneau X, Morisset S, Tardivel-Lacombe J, Gbahou F, Ganellin CR, Stark H, Schunack W, Schwartz JC, Arrang JM (2000) Distinct pharmacology of rat and human histamine H(3) receptors: role of two amino acids in the third transmembrane domain. Br J Pharmacol 131(7):1247–1250. doi:10.1038/sj.bjp.0703712
Liu C, Wilson SJ, Kuei C, Lovenberg TW (2001) Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther 299:121–130
Macarthur H, Wilken GH, Westfall TC, Kolo LL (2011) Neuronal and non-neuronal modulation of sympathetic neurovascular transmission. Acta Physiol 203(1):37–45. doi:10.1111/j.1748-1716.2010.02242.x
Middendorff R, Muller D, Mewe M, Mukhopadhyay AK, Holstein AF, Davidoff MS (2002) The tunica albuginea of the human testis is characterized by complex contraction and relaxation activities regulated by cyclic GMP. J Clin Endocrinol Metab 87(7):3486–3499
Mondillo C, Pagotto RM, Piotrkowski B, Reche CG, Patrignani ZJ, Cymeryng CB, Pignataro OP (2009) Involvement of nitric oxide synthase in the mechanism of histamine-induced inhibition of Leydig cell steroidogenesis via histamine receptor subtypes in Sprague–Dawley rats. Biol Reprod 80(1):144–152. doi:10.1095/biolreprod.108.069484
Nemetallah BR, Howell RE, Ellis LC (1983) Histamine H1 receptors and prostaglandin-histamine interactions modulating contractility of rabbit and rat testicular capsules in vitro. Biol Reprod 28(3):632–635
O’Reilly M, Alpert R, Jenkinson S, Gladue RP, Foo S, Trim S, Peter B, Trevethick M, Fidock M (2002) Identification of a histamine H4 receptor on human eosinophils—role in eosinophil chemotaxis. J Recept Signal Transduct Res 22(1–4):431–448
Oliva A, Multigner L (2006) Ketotifen improves sperm motility and sperm morphology in male patients with leukocytospermia and unexplained infertility. Fertil Steril 85(1):240–243. doi:10.1016/j.fertnstert.2005.06.047
Phillips MJ, Meyrick Thomas RH, Moodley I, Davies RJ (1983) A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin. Br J Clin Pharmacol 15(3):277–286
Silva Junior ED, Caricati-Neto A, Jurkiewicz NH, Jurkiewicz A (2012) Functional antagonism of amphetamine versus ethanol on adrenergic neurotransmission in vas deferens of adolescent rats. Eur J Pharmacol 674(2–3):415–421. doi:10.1016/j.ejphar.2011.10.043
Silva Junior ED, Souza BP, Rodrigues JQ, Caricati-Neto A, Jurkiewicz A, Jurkiewicz NH (2013) Functional characterization of acetylcholine receptors and calcium signaling in rat testicular capsule contraction. Eur J Pharmacol. doi:10.1016/j.ejphar.2013.07.007
Smits RA, Leurs R, de Esch IJ (2009) Major advances in the development of histamine H4 receptor ligands. Drug Discov Today 14(15–16):745–753
Todorov S, Zamfirova R (1985) Histaminergic agents can modulate adrenergic smooth muscle neurotransmission. Methods Find Exp Clin 7(7):357–360
Vassilev P, Staneva-Stoytcheva D, Mutafova-Yambolieva V (1991) Do H3-receptors participate in the effects of histamine on electrically-evoked contractions of rat vas deferens? Gen Pharmacol 22(4):643–645
Westfall TD, Westfall DP (2001) Pharmacological techniques for the in vitro study of the vas deferens. J Pharmacol Toxicol Methods 45(2):109–122
Wulff BS, Hastrup S, Rimvall K (2002) Characteristics of recombinantly expressed rat and human histamine H3 receptors. Eur J Pharmacol 453(1):33–41
Zamfirova R, Todorov S (1995) Receptor subtypes involved in the modulatory action of histamine on the contractility of the rat vas deferens. Inflamm Res 44(Suppl 1):S92–S93
Acknowledgments
Thanks are due to Haydée Reuter and Maria de Lourdes dos Santos for helping in the experiments and to the CAPES, FAPESP, and CNPq (Brazil) for financial support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
da Silva Júnior, E.D., Rodrigues, J.Q.D., de Souza, B.P. et al. A comparison of histamine effects on the sympathetic neurotransmission of testicular capsule and rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 387, 719–731 (2014). https://doi.org/10.1007/s00210-014-0979-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-014-0979-z