Age‐related changes in purinergic and adrenergic components of sympathetic neurotransmission in guinea‐pig seminal vesicles

Abstract

1 Purinergic and adrenergic components of sympathetic neurotransmission and contractile responses to exogenous a,b-methylene ATP and noradrenaline have been investigated in the seminal vesicles of 1-day (new-born), 2-weeks (young), 12-weeks (adult) and 2-years old (aged) guinea-pigs. 2 In seminal vesicles of new-born guinea-pigs electrical ®eld stimulation (EFS; 80 V, 0.5 ms for 30 s, 2 ± 32 Hz) evoked tonic frequency-related contractions. In 2-weeks old guinea-pigs the tonic contraction masked an initial phasic component of the neurogenic responses, whereas in 12-weeks and 2-years old guinea-pigs, neurogenic responses were biphasic, a phasic response being followed by a tonic contraction. In all experimental groups, prazosin (10 76 M) blocked the tonic contraction while desensitization of P2X receptors by a,b-methylene ATP (10 74 M) abolished the phasic responses. 3 The phasic purinergic component of the neurogenic response was signi®cantly higher in 12-weeks and 2-years old animals, compared with 2-weeks old guinea-pigs. At 32 Hz phasic contractions were (mN mg 71 tissue): 0.047+0.012, 0.018+0.040 and 0.147+0.026 in 2-weeks, 12-weeks and 2-years old guinea-pigs, respectively. In contrast, the tonic adrenergic component of the neurogenic contraction signi®cantly declined at 12-weeks and 2-years compared with 2-weeks old guinea-pigs. 4 Contractile responses (mN mg 71 tissue) to the highest concentration of a,b-methylene ATP tested were signi®cantly higher in 2-weeks (0.248+0.022) than in 1-day old animals (0.113+0.012) and decreased in 12-weeks (0.163+0.016) and 2-years old guinea-pigs (0.200+0.008). The pD 2 values for the purinoceptor agonist were also signi®cantly lower in adult (4.74+0.20) and aged guinea-pigs (5.22+0.08) compared with 2-weeks old animals (5.91+0.27). Conversely, responses to the highest concentration of noradrenaline gradually decreased with age, without signi®cant changes in the pD 2 values. Contractile responses to KCl (240 mM) did not di er signi®cantly between the experimental groups. 5 These results demonstrate age-related changes in purinergic and adrenergic components of sympathetic neurotransmission in the guinea-pig seminal vesicles. The purinergic component is absent in new-born animals and it appears fully developed in adult and old guinea-pigs, while the adrenergic component decreases with age. Pre-and postjunctional mechanisms contributing to the age-related changes of sympathetic neurotransmission are discussed.

Purinergic signalling during development and ageing

“…The authors speculated that this may reflect the increase in overactive bladder in ageing humans. In old guinea pigs, the purinergic component of sympathetic cotransmission was dominant in seminal vesicles [353]. P2X4 receptor expression increased in pancreatic islets in old age, but P2Y 1 receptor expression was lost [354].…”

Evidence that Adrenergic and Cholinergic but Not Capsaicin-Sensitive Nerves Are Involved in the Nerve-Mediated Contraction of the Guinea Pig Seminal Vesicle

“…Responses of both types of preparation were practically reproducible upon repeated stimulations, 3 cycles 30 min apart (tables 1, 2). Responses evoked under the conditions of the present study did not show a clear-cut biphasic character [6]. …”

“…Yet, there is debate as to the mediating role of noradrenaline in the nerve-mediated contraction of the GPSV, on the basis of the lack of effect or variable effects of different adrenergic α-receptor antagonists [3,4,5]. This led to the conclusion that the excitatory response is mediated by non-adrenergic, non-cholinergic neurons, although an inhibitory effect of α-receptor antagonism was reported by Pinna et al [6]. Purinergic nerves (mediating contraction) have consistently been reported to participate in the excitatory motor response of the GPSV [6,7].…”

“…While the functional innervation of the GPSV by purinergic nerves is not debated [6,7], the mediating role of noradrenergic nerves has been a matter of controversy (see Introduction). Our current data clearly indicate that norepinephrine contributes to the response (both longitudinal and circular) to field stimulation, since the adrenergic α-receptor antagonist phentolamine strongly reduces the response.…”

“…This led to the conclusion that the excitatory response is mediated by non-adrenergic, non-cholinergic neurons, although an inhibitory effect of α-receptor antagonism was reported by Pinna et al [6]. Purinergic nerves (mediating contraction) have consistently been reported to participate in the excitatory motor response of the GPSV [6,7]. Acetylcholine causes contraction of this organ (see among others Stjernquist et al [4]), but the cholinergic antagonist atropine has been reported to be without effect on nerve-mediated responses [4].…”