Biomedical subjects

Sabatino Ventura

Publications and source records attributed to Sabatino Ventura.

9 recordsLinked to original sources

PubMed2006

Alpha1L-adrenoceptors mediate contractions of the isolated mouse prostate.

The subtype of alpha1-adrenoceptor mediating noradrenaline-induced contractile responses in isolated mouse prostate glands was investigated. Adrenoceptor agonists were able to produce concentration-dependent contractions with the following rank order of potency: adrenaline > or = noradrenaline > or = clonidine = phenylephrine > dopamine > or = isoprenaline. Concentration-response curves to noradrenaline of the prostatic smooth muscle were antagonised by prazosin, N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine (RS-17053), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), tamsulosin and yohimbine with mean antagonist affinity estimates (pA2 or apparent pKB) of 8.12+/-0.10, 6.56+/-0.11, 8.38+/-0.06, 10.14+/-0.19 and 7.38+/-1.36 respectively. Propranolol (1 microM) had no antagonist activity (P = 0.994, n = 6). Yohimbine (0.01, 0.1, 1 microM) had no antagonist activity in the presence of prazosin (0.1 microM) (P > or = 0.059). The results obtained indicate that alpha1-adrenoceptors mediate the contractile response in isolated preparations of the mouse prostate. Furthermore, the particular subtype of alpha1-adrenoceptor mediating the response to exogenously administered noradrenaline corresponds to the alpha1L-subtype, the same subtype as that which has been shown to mediate noradrenaline-induced contractile activity in the human prostate.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2006

Saw palmetto is an indirectly acting sympathomimetic in the rat-isolated prostate gland.

BACKGROUND: To investigate whether saw palmetto that inhibits alpha1-adrenoceptor binding in vitro affects contractility of the rat prostate gland. METHODS: The effects of a commercially available saw palmetto extract were examined on the contractility of rat-isolated prostate glands. The extract was tested in the presence and absence of phentolamine, prazosin, yohimbine, propranolol, hexamethonium, cocaine, desipramine, nifedipine, guanethidine, atropine, and alpha,beta-methylene ATP to evaluate the mechanism of action. Isolated preparations of rat vas deferens and bladder were used for comparison. RESULTS: Unexpectedly, saw palmetto extract caused contractions of the rat prostate gland that could be attenuated by prazosin, phentolamine, nifedipine, guanethidine, cocaine, and desipramine but not by any of the other pharmacological tools. Similar contractile effects were observed in rat-isolated vas deferens preparations but not in rat-isolated bladder preparations. CONCLUSIONS: In the rat prostate gland, saw palmetto extract causes indirect alpha1-adrenoceptor-mediated contractions via the release of noradrenaline from sympathetic neurons.

Amphetamine↗

PubMed2005

Pharmacological characterisation of a neurotoxin from the venom of Boiga dendrophila (mangrove catsnake).

In this study, we have pharmacologically characterised boigatoxin-A, a three finger toxin isolated from the venom of the colubrid, Boiga dendrophila (Mangrove catsnake). In the chick biventer cervicis nerve-muscle preparation boigatoxin-A (1 microM) displayed poorly reversible postsynaptic blockade as evidenced by the inhibition of indirect (0.1 Hz, 0.2 ms, supramaximal V) twitches and responses to exogenous acetylcholine (1 mM) and carbachol (20 microM). Boigatoxin-A (0.3-0.5 microM) caused a concentration-dependent depression of the maximum response of cumulative concentration response curves to CCh (0.6-80 microM). Boigatoxin-A (1 microM) induced readily reversible inhibition of electrically evoked (0.2 Hz, 0.3 ms, 70-100 V) twitches of the prostatic segment of the rat vas deferens. This inhibition was not significantly attenuated by 8-phenyltheophylline (20 microM) or idazoxan (1 microM). Boigatoxin-A (1 microM) did not affect alpha,beta-mATP (10 microM) or noradrenaline (25 microM) responses in unstimulated epididymal segments of the rat vas deferens. Our data suggests that this toxin has weak postsynaptic neurotoxicity in skeletal muscle and also prejunctional neurotoxic activity in the smooth muscle of the rat vas deferens to inhibit the release of neurotransmitter(s), but not via prejunctional purinergic or adrenergic receptors. This is the first report of such activity for a toxin isolated from snake venom and reinforces the largely untapped potential of colubrid venoms.

Animals↗

PubMed2005

A biochemical and pharmacological examination of Rhamphiophis oxyrhynchus (Rufous beaked snake) venom.

The venom of R. oxyrhynchus, a member of the psammophiine subfamily of the colubrid assemblage, was examined for biological activity using biochemical and pharmacological techniques. Venom displayed a high protein content, a complex electrophorectic profile and PLA2 activity but no detectable proteolytic or haematological activities. In the chick biventer cervicis nerve muscle preparation, venom (1-10 microg/ml) displayed postsynaptic neurotoxic activity as evidenced by inhibition of indirect (0.1 Hz, 0.2 ms, supramaximal V) twitches and responses to exogenous acetylcholine (1 mM) and carbachol (20 microM). This inhibitory effect was poorly reversible by washing. Venom (30-50 microg/ml) caused a rapid and readily reversible inhibition of direct (0.1 Hz, 2 ms, supramaximal V) twitches of the chick biventer cervicis nerve muscle preparation without morphological changes to the muscle fibers. Venom (30-100 microg/ml) inhibited electrically-evoked (0.2 Hz, 0.3 ms, 70-100 V) twitches of the prostatic segment of the rat vas deferens. This inhibitory effect was not significantly attenuated by 8-phenyltheophylline (8-PT; 20 microM), idazoxan (1 microM), a combination of ranitidine (0.2 microM) and thioperamide (10 microM) or capsazepine (10 microM). Venom (5 mg/kg) induced hypotension with subsequent cardiovascular collapse in the anaesthetised rat. The cardiovascular collapse was prevented by artificial respiration of the animals prior to venom administration. The biological activities demonstrated by R. oxyrhynchus venom may aid in prey envenomation strategies such as prey immobilisation. This study provides further evidence that colubrid venoms are comprised of multiple components which can display a variety of actions, some of which may be novel, therefore reinforcing the largely untapped potential of colubrid venoms.

Animals↗

PubMed2005

Current models of human prostate contractility.

1. The human prostate is a compact gland contributing to seminal fluid. With increasing age, most humans will develop benign prostatic hyperplasia, a condition of prostatic enlargement and contractility that leads to occlusion of the urethra. Over many years, investigators have used a variety of animal and cell culture models to elucidate some of the contractile and proliferative mechanisms that may be associated with the development of this condition. 2. This review briefly assesses the current state of knowledge of the mechanisms underlying human prostatic contractility and compares it with that of animal and cell culture models. It is not intended as a comprehensive methodological review, nor is it intended to indicate our preferences for either model. Our aim is to correlate findings from animal and cell culture models with the current understanding of human prostate contractility. 3. We hope that the present review will increase awareness of the suitability of the current models in developing our understanding of benign prostatic hyperplasia.

Animals↗

PubMed2004

Adenosine 5'-triphosphate and noradrenaline are excitatory cotransmitters to the fibromuscular stroma of the guinea pig prostate gland.

Immunohistochemical studies demonstrated abundant P2X(1)-receptor immunoreactivity colocalized with alpha-actin within the fibromuscular stroma of the guinea pig prostate. P2X(2)-, P2X(3)- and P2X(4)-receptor immunoreactivity was absent. alphabetamethylene Adenosine 5'-triphosphate (ATP) attenuated contractile responses to electrical field stimulation (50 V, 0.5 ms, 5-20 Hz) in the absence and presence of prazosin (0.3 microM). Responses to 1-2 Hz were unaffected. ARL 67156 (6-N, N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5-triphosphate; 100 microM) enhanced contractile responses to electrical field stimulation (50 V, 0.5 ms, 10-20 Hz). Concentration-response curves to exogenously applied ATP analogues on unstimulated preparations elicited concentration-dependent suramin (100 microM)-sensitive contractions. The rank order of potency was: alphabetamethylene ATP>2methylthio ATP=betagammamethylene ATP>adenosine 5'-diphosphate (ADP)=ATP. Adenosine and adenosine 5'-monophosphate (AMP) did not produce contractile responses. These results demonstrate the presence of functional P2X(1)-receptors within the fibromuscular stroma of the guinea pig prostate and suggest a cotransmitter role for ATP with noradrenaline during high-frequency stimulation.

Actins↗

PubMed2003

Adenosine 5'-triphosphate (ATP) is an excitatory cotransmitter with noradrenaline to the smooth muscle of the rat prostate gland.

1. This study investigated whether adenosine 5'-triphosphate (ATP) is involved in neurotransmission to the rat prostate gland. 2. Fluorescence immunohistochemistry carried out on formaldehyde-fixed and frozen sections of rat prostate showed immunoreactivity for the P2X(1)-receptor in the fibromuscular stroma surrounding the secretory acini but not in the glandular epithelium. P2X(2)-, P2X(3)-, P2X(4)- and P2X(7)-receptors were immunonegative in the rat prostate stroma. Double-staining procedures showed P2X(1)-receptor immunoreactivity to be colocalized with alpha-actin immunoreactivity. 3. Isolated organ bath studies investigated whether drugs, which modify purinergic mechanisms, are able to affect contractility of the rat prostate gland. Suramin (100 micro M) and alphabetamethylene ATP (10 micro M) inhibited contractile responses to trains of electrical-field stimulation (70 V, 0.5 ms, 0.1-2 Hz) in the absence and presence of prazosin (300 nM). Responses to 5-20 Hz were unaffected by suramin or alphabetamethylene ATP. 4. Exogenous application of ATP analogues to unstimulated isolated preparations of rat prostate produced concentration-dependent suramin (100 micro M) sensitive transient contractions with a relative order of potency: alphabetamethylene ATP>betagammamethylene ATP>ATP. 5. Adenosine and adenosine 5'-monophosphate (AMP) did not produce contractile responses. 6. These results suggest that P2X(1)-receptors for ATP, which mediate contractions are present in the fibromuscular stroma of the rat prostate. The relative order of potency of ATP analogues in producing contractions of the rat prostate is consistent with the activation of P2X(1)-receptors. Inhibition by suramin and alphabetamethylene ATP of electrically evoked nerve-mediated contractions of the rat prostate implies that ATP contributes to this contractile response and is therefore a cotransmitter with noradrenaline during low-frequency stimulation.

Adenosine Triphosphate↗

PubMed2002

Protein kinase C and the sub-sensitivity and sub-reactivity of the diabetic rat prostate gland to noradrenaline.

Concentration-response curves to noradrenaline (1 nM-100 microM) were obtained in prostates from 6-week streptozotocin diabetic, insulin-treated diabetic or control rats. Compared to the curve obtained in controls, those obtained in prostates from diabetic and insulin-treated diabetic rats were shifted rightward. The alpha1-adrenoceptor antagonist, prazosin (100 nM), caused a rightward shift of the curves in prostates from all groups. In contrast, the uptake 1 inhibitor, nisoxetine (300 nM), only produced a leftward shift of the curves in prostates from control and insulin-treated diabetic rats. However, frequency-response curves obtained in prostates from both control and diabetic rats were shifted leftward by nisoxetine (300 nM). The concentration-response curve to the alpha1-adrenoceptor agonist, methoxamine (10 nM-100 microM), obtained in prostates from diabetic rats was shifted rightward compared with controls. Calphostin C (500 nM), a protein kinase C inhibitor, caused a leftward shift of the curve in prostates from diabetic, but not control, rats. The protein kinase C inhibitor, bisindolylmaleimide I (500 nM), beta-adrenoceptor antagonist, propranolol (500 nM) and muscarinic cholinoceptor antagonist, atropine (300 nM), had no effect on the noradrenaline concentration-response curves of prostates from control or diabetic rats. Our results suggest that diabetes reduces the sensitivity and reactivity of the prostate to noradrenaline-induced stimulation, and this reduction may be due to changes in protein kinase C activity.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Evaluation of the mouse prostate as a suitable model for the study of human prostate function.

INTRODUCTION: Research into prostate development and function is mainly carried out in rats and guinea pigs. While these animals have proven to be good models of human prostate function, their use is limited when compared with what could be achieved using the various currently available gene knockout mice. This study aimed to ascertain whether the mouse prostate was a viable model for studying human prostate function. METHODS: Sections from mouse prostate glands were histochemically processed to visualise the neurotransmitters and receptors present. Isolated organ bath studies were conducted in Krebs-Henseleit solution at 37 degrees C to delineate the physiological mechanisms involved in contractility. RESULTS: Positive histochemical staining for noradrenaline and acetylcholinesterase (AChE) was observed in the fibromuscular stroma. AChE-positive staining was also observed in epithelial cells lining prostatic acini. Immunoreactivity to P2X(1) and P2X(7) purinoceptors was observed in the fibromuscular stroma and immunoreactivity to P2X(4) purinoceptors in the glandular epithelium. Positive immunostaining for neuropeptide Y, big endothelin, calcitonin gene-related peptide (CGRP), substance P, and neurokinin A was observed in the fibromuscular stroma. Frequency-response curves (1.0 ms pulse duration, 60 V, 0.1-20 Hz) to electrical field stimulation yielded frequency-dependent contractions that were attenuated by tetrodotoxin (P < .001), guanethidine (P < .001), and prazosin (P = .01). Suramin (P = .21), alpha,beta-methylene ATP (P = .84), and atropine (P = .76) caused no significant effects. Concentration-response curves to endogenously administered phenylephrine yielded concentration-dependent contractions (pEC(50) = 6.1 +/- 0.3, maximum response 0.20 +/- 0.03 g), which were attenuated by prazosin (P < .001). DISCUSSION: Histochemistry suggests that mouse prostates have a similar innervation to that of humans and other laboratory animals. Furthermore, responses to nerve stimulation are noradrenergic and mediated by alpha(1)-adrenoceptors. Therefore, the mouse prostate is a suitable model for human prostate function and a viable isolated preparation for contractility studies.

Acetylcholinesterase↗